SEMINAR VINDEREN 23 JANUAR NEVROPSYKOLOGISKE OG NEVROBIOLOGISKE ASPEKTER VED DEPRESJON: FRA LABORATORIET TIL KLINIKKEN.

Transcription

1 SEMINAR VINDEREN 23 JANUAR NEVROPSYKOLOGISKE OG NEVROBIOLOGISKE ASPEKTER VED DEPRESJON: FRA LABORATORIET TIL KLINIKKEN. Nils Inge Landrø

2 SENTRALE NEVROPSYKOLOGISKE/KOGNITIVE FUNKSJONSOMRÅDER. -KONSENTRASJON/OPPMERKSOMHET -PSYKOMOTORISK TEMPO -ARBEIDSHUKOMMELSE -INNLÆRING/LANGTIDSHUKOMMELSE (SPRÅKLIG VS. IKKE-SPRÅKLIG MATERIALE) -ULIKE ASPEKTER VED EKSEKUTIVE FUNKSJONER -GENERELLE KOGNITIVE (EVNE) FUNKSJONER. ----EKSEMPLER OPERASJONALISERINGER/TESTER/PARADIGMER

3 COGNITIVE/NEUROPSYCHOLOGICAL FUNCTIONS (SELECTIVE ATTENTION)

4 COGNITIVE/NEUROPSYCHOLOGICAL FUNCTIONS.

5 COGNITIVE/NEUROPSYCHOLOGICAL FUNCTIONS.

6 COGNITIVE/NEUROPSYCHOLOGICAL FUNCTIONS (Working memory).

7 THE NEUROPSYCHOLOGY OF MAJOR DEPRESSIVE DISORDER (MDD).

8 Nevrobiologiske korrelater/mekanismer Funksjonelle hjerneavbildningsstudier har vist at under pågående depresjon skjer det en hypoaktivering i deler av prefrontale cortex og anterior cingulum, strukturer som er spesielt involvert i kognitive funksjoner som arbeidshukommelse, oppmerksomhet og eksekutive funksjoner. Mer spesifikt har Mayberg et al. foreslått en modell hvor depresjonsavhengig kognitiv reduksjon forklares som redusert oppmerksomhetskontroll pga. hypoaktivering i nevrale nettverk som blant annet omfattter dorsolaterale prefrontale cortex og anterior cingulum (Kessler & Mayberg, Nature Neuroscience, 2007, 10,

9 Nevrobiologiske korrelater/mekanismer

10 STATE OR TRAIT? Taken together, these findings suggest that the tradional view of neuropsychological deficits in affective disorder generally minor, occasionally more marked, but always restricted to periods of illness- might be something of an oversimplification. McKay et al. (1995). British Journal of Psychiatry

11 Nevrobiologiske korrelater/mekanismer En hypotese er at negative effekter av stress hormoner knyttet til gjentatte depressive episoder kan medføre hjerneorganiske forandringer og derved stabile nevropsykologiske dysfunksjoner.

12 Nevrobiologiske korrelater/mekanismer

13 EFFECTS OF DEPRESSION ON THE BRAIN.

14 DEPRESSION/ ATTENTION BIAS/ EMOTION INFORMATION PROCESSING

15 DEPRESSION/ ATTENTION BIAS/ EMOTION INFORMATION PROCESSING

16 DEPRESSION/ ATTENTION BIAS/ EMOTION INFORMATION PROCESSING

17 EMOTION INFORMATION PROCESSING Clinically depressed subjects orient their attention toward sad faces in dot-probe tasks. A bias towards sad faces has also been reported in remitted depressed patients, suggesting alterations in processing of emotional salient information being a trait marker for depression Gotlib et al. (2004). Attentional biases for negative interpersonal stimuli in depressed and nondepressed individuals. J. of Abnormal Psychology, 113, Joorman, J. & Gotlib, I.H. (2007). Selective attention to emotional faces following recovery form depression. J. of Abnormal Psychology, 116, 80-85

18 Browning, Holmes, Charles, Cowen & Harmer (2012). Using attentional bias modification as a cognitive vaccine against depression. Biological Psychiatry, 72; Background Negative attentional biases are thought to increase the risk of recurrence in depression, suggesting that reduction of such biases may be a plausible strategy in the secondary prevention of the illness. However, no previous study has tested whether reducing negative attentional bias causally affects risk factors for depressive recurrence. The current experimental medicine study reports the effects of a computerized attentional bias modification (ABM) procedure on intermediate measures of the risk of depressive recurrence (residual depressive symptoms and the cortisol awakening response) in patients with recurrent depression. Methods Sixty-one patients with at least two previous episodes of depression who were currently in remission were randomized to receive either an active (positive) or placebo computer-based ABM regime. The ABM regime presented either pictures of faces or words. Residual depressive symptoms, measured using the Beck Depression Inventory and the cortisol awakening response were measured immediately before and after completion of the bias modification and then again after 4 weeks' follow-up. Results Positive, face-based ABM reduced both measures of recurrence risk (Beck Depression Inventory and cortisol awakening response). This effect occurred during the month following completion of bias modification. Wordbased modification did not influence the outcome measures. Conclusions Positive face-based ABM was able to reduce intermediate measures of recurrence risk in previously depressed patients. These results suggest that ABM may provide a cognitive vaccine against depression and offer a useful strategy in the secondary prevention of the illness.

19 DEPRESSION/ ATTENTION BIAS/ EMOTION INFORMATION PROCESSING

20 PERSPECTIVE I: A NEUROPSYCHOLOGICL MODEL OF ANTIDEPRESSANT DRUG ACTION Harmer et al. (2003) Am. J. of Psychiatry, 160, OBJECTIVE: Antidepressants that increase serotonin or norepinephrine in the brain are effective in treating depression, but there is no neuropsychological account of how these changes relieve depressive states. Cognitive theories suggest that biases in information processing lead depressed patients to make unrealistically negative judgments about themselves and the world. METHOD: A single dose of the noradrenergic antidepressant reboxetine or placebo was administered to 24 healthy volunteers. Effects on emotional processing were assessed through facial expression recognition, emotional categorization, and emotional memory. RESULTS: On the three measures, reboxetine biased perception toward positive, rather than negative, information in the absence of changes in nonemotional performance or mood. CONCLUSIONS: These results suggest that a single dose of an antidepressant can increase the processing of positively valenced material in nondepressed volunteers. Antidepressants may therefore work in a manner similar to that of psychological treatments that aim to redress negative biases in information processing.

21

22 Perspective II: From vulnerability to plasticity. Possible Implictions for treatment Fox et al. (2011). The serotonin tranporter gene alters sensitivity to attenton bias modification: evidence for a plasticity gene. Biological Psychiatry, 7, Background Attention bias modification (ABM) procedures have been shown to modify biased attention with important implications for emotional vulnerability and resilience. The use of ABM to reduce potentially toxic biases, for instance, is a newly emerging therapy for anxiety disorders. A separate line of gene-byenvironment interaction research proposes that many so-called vulnerability genes or risk alleles are better seen as plasticity genes, as they seem to make individuals more susceptible to environmental influences for better and for worse. Methods A standard ABM procedure was used with a sample of 116 healthy adults. Participants were randomly assigned to one of two training groups. One received an ABM procedure designed to induce a bias in attention toward negative material, while the other was trained toward positive pictures. Individuals with low- and high-expressing forms of the serotonin transporter gene (5-HTTLPR) were compared. Results Those with a low-expression form (S/S, S/Lg, or Lg/Lg) of the 5-HTTLPR gene developed stronger biases for both negative and positive affective pictures relative to those with the high-expression (La/La) form of the gene. Conclusions Here, we report the first evidence that allelic variation in the promotor region of the 5-HTTLPR gene predicts different degrees of sensitivity to ABM. These results suggest a potential cognitive mechanism for the gene-by-environment interactions that have been found in relation to the serotonin transporter gene. Variation on this genotype may therefore determine who will benefit most (and least) from therapeutic interventions, adversity, and supportive environments.

23 EMOTIONAL DYSREGULATION: BASIC PROBLEM IN AFFECTIVE DISORDERS.

24 DEPRESSION/ ATTENTION BIAS/ EMOTION INFORMATION PROCESSING

25

26

27

28