[Sleep, learning and memory: relevance for psychiatry and psychotherapy]. / Schlaf, Lernen und Gedächtnis: Relevanz für Psychiatrie und Psychotherapie.

BACKGROUND: Sleep has been identified as a state that optimizes the consolidation of newly acquired information in the memory. Sleep disturbances might essentially contribute to memory impairment in relevant psychiatric disorders, such as major depression and schizophrenia. METHODS: This article provides a brief review of the latest research results on sleep and its association with memory consolidation. RESULTS AND CONCLUSION: Specific disturbances of sleep structure are associated with particular memory deficits in psychiatric patients. Effective treatment of sleep disorders should not only improve signs of sleep but should also heal associated memory impairments.

Sleep enhances exposure therapy.

BACKGROUND: Sleep benefits memory consolidation. Here, we tested the beneficial effect of sleep on memory consolidation following exposure psychotherapy of phobic anxiety. METHOD: A total of 40 individuals afflicted with spider phobia according to DSM-IV underwent a one-session virtual reality exposure treatment and either slept for 90 min or stayed awake afterwards. RESULTS: Sleep following exposure therapy compared with wakefulness led to better reductions in self-reported fear (p = 0.045, d = 0.47) and catastrophic spider-related cognitions (p = 0.026, d = 0.53) during approaching a live spider, both tested after 1 week. Both reductions were associated with greater percentages of stage 2 sleep. CONCLUSIONS: Our results indicate that sleep following successful psychotherapy, such as exposure therapy, improves therapeutic effectiveness, possibly by strengthening new non-fearful memory traces established during therapy. These findings offer an important non-invasive alternative to recent attempts to facilitate therapeutic memory extinction and consolidation processes with pharmacological or behavioral interventions.

A genome-wide survey and functional brain imaging study identify CTNNBL1 as a memory-related gene.

Unbiased genome-wide screens combined with imaging data on brain function may identify novel molecular pathways related to human cognition. Here we performed a dense genome-wide screen to identify episodic memory-related gene variants. A genomic locus encoding the brain-expressed beta-catenin-like protein 1 (CTNNBL1) was significantly (P=7 × 10(-8)) associated with verbal memory performance in a cognitively healthy cohort from Switzerland (n=1073) and was replicated in a second cohort from Serbia (n=524; P=0.003). Gene expression studies showed CTNNBL1 genotype-dependent differences in beta-catenin-like protein 1 mRNA levels in the human cortex. Functional magnetic resonance imaging in 322 subjects detected CTNNBL1 genotype-dependent differences in memory-related brain activations. Converging evidence from independent experiments and different methodological approaches suggests a role for CTNNBL1 in human memory.

Aversive stimuli lead to differential amygdala activation and connectivity patterns depending on catechol-O-methyltransferase Val158Met genotype.

The functional Val158Met polymorphism in the gene coding for the catechol-O-methyltransferase (COMT), the major enzyme degrading the catecholaminergic neurotransmitters dopamine, norepinephrine, and epinephrine, has been associated with differential reactivity in limbic and prefrontal brain areas in response to aversive stimuli. However, studies on COMT-genotype effects on activity of the amygdala, a brain region centrally involved in affective processing, have yielded inconsistent results. Here we investigated the impact of the COMT Val158Met polymorphism on amygdala activity and connectivity during processing of emotional and neutral pictures using functional magnetic resonance imaging (fMRI) in 56 healthy participants. Homozygosity for the low-activity Met allele was positively correlated with increased activation in the right amygdala in response to unpleasant, but not pleasant pictures. In addition, the Met allele exerted an additive effect on the positive connectivity between the right amygdala and orbitofrontal regions. Our results support previous reports of a COMT-genotype-dependent difference in amygdala responsivity as well as connectivity, and highlight the importance of naturally occurring genetic variations in the catecholaminergic system for neural activity underlying affective processing.

Imaging genetics of cognitive functions: Focus on episodic memory.

Human cognitive functions are highly variable across individuals and are both genetically and environmentally influenced. Recent behavioral genetics studies have identified several common genetic polymorphisms, which are related to individual differences in memory performance. In addition, imaging genetics studies are starting to explore the neural correlates of genetic differences in memory functions on the level of brain circuits. In this review we will describe how functional magnetic resonance imaging (fMRI) can be used to validate and extend findings of behavioral genetics studies of episodic memory and give examples of recent advances in this new and exciting research field. In addition, we will present advantages and problems related to the different sensitivity of behavioral- vs. imaging genetics studies and discuss possible methodological approaches for an appropriate evaluation and integration of the results. Although the field of imaging genetics of episodic memory is still young, it already became clear that imaging methods have a large potential to enhance our understanding of the neural mechanisms that underlie genetic differences in memory.

A genetic variation of the noradrenergic system is related to differential amygdala activation during encoding of emotional memories.

Emotionally arousing events are typically well remembered, but there is a large interindividual variability for this phenomenon. We have recently shown that a functional deletion variant of ADRA2B, the gene encoding the alpha2b-adrenergic receptor, is related to enhanced emotional memory in healthy humans and enhanced traumatic memory in war victims. Here, we investigated the neural mechanisms of this effect in healthy participants by using fMRI. Carriers of the ADRA2B deletion variant exhibited increased activation of the amygdala during encoding of photographs with negative emotional valence compared with noncarriers of the deletion. Additionally, functional connectivity between amygdala and insula was significantly stronger in deletion carriers. The present findings indicate that the ADRA2B deletion variant is related to increased responsivity and connectivity of brain regions implicated in emotional memory.

PreproTRH(158-183) fails to affect pituitary-adrenal response to CRH/vasopressin in man: a pilot study.

Non-glucocorticoid inhibitors of the HPA-system are of utmost interest in the treatment of diseases with impaired regulation of this system, like the metabolic syndrome and depression. In rats, a fragment of the thyreotropin-releasing hormone (TRH) preprohormone, preproTRH((178-199)), has been demonstrated to inhibit basal and stimulated secretion of cortisol. Our pilot study aimed to explore the first time similar effects of the homologue peptide preproTRH((158-183)) in healthy humans. In a double-blind within-subject comparison, eight healthy young men were infused intravenously with placebo and preproTRH((158-183)) at varying doses of 5, 10, 25 and 50 mg/kg of body weight. After 15 min of infusion a corticotropin-releasing hormone (CRH)/vasopressin-test was performed. Plasma concentrations of pituitary hormones and free thyroxine, blood pressure, heart rate and feelings of activation and mood were assessed repeatedly at close intervals. Individual hormone profiles and collapsed data across all doses did not reveal any effects of preproTRH((158-183)) on HPA-activity, although it increased TSH and fT4, stimulated the release of GH and increased systolic blood pressure in the course of the experiment (p<0.05, for all effects). Self-reports indicated enhanced feelings of activation and general well-being following preproTRH (p<0.05). Our data exclude a substantial inhibitory effect of preproTRH((158-183)) on HPA secretory activity and, thus, contrast with findings in rats. In humans, the peptide appears to even exert an albeit weak stimulatory effect on autonomic stress systems as indicated by increased cardiovascular activity in combination with enhanced subjective arousal.

Cardiovascular and neuroendocrine activity in preschool children: comparison between day-care and home levels.

Thirty boys and 30 girls at nine day-care centers were examined at the mean age of 3.5 and 5.5 with regard to systolic and diastolic blood pressure, heart rate and neuroendocrine activity (urinary catecholamines and cortisol) during a day at their day-care center and in their home, respectively. Compared to home levels, day-care was associated with increased heart rate, epinephrine and norepinephrine excretion and decreased cortisol levels. Systolic blood pressure decreased at the day-care centers at the age of 3.5 and increased at the age of 5.5. No significant sex differences were found. The possible role of mental and physical arousal and the dissociation between the sympathetic-adrenal medullary and the pituitary-adrenal cortical responses are discussed.

Clinical significance of outcome in long-term follow-up of borderline patients at a day hospital.

All borderline patients admitted at a day hospital during a 6-year period were followed up with a postal questionnaire after 3-10 years. Patients who had chosen to leave the treatment within 4 months were analyzed as a separate group, and these drop-outs and the remaining patients were compared with a group of well-adjusted people who were assumed to represent the functional norm. The patients who remained in treatment were clearly posited at a level of functioning between the norm and the drop-outs, although the variation among them was quite large. Depending on the stringency and content of the criterion of clinical significance, 25-75% of the patients remaining in treatment fell within the range of the norm group versus 20-50% of the drop-outs. The patients who had benefited most since termination had differed favorably from the other patients already at admission to treatment, but not as much as had the drop-outs. The drop-outs, however, at admission also had more ambivalent or negative attitudes towards treatment.

Physiological reactivity and Type A behavior in preschool children: a longitudinal study.

Measurements of Type A behavior were related to cardiovascular (systolic and diastolic blood pressure, heart rate) and neuroendocrine (urinary catecholamines and cortisol) reactivity in 30 male and 30 female preschool children during various active conditions at their mean ages of 3.5, 4.5, 5.5, and 6.5. Significant elevations of physiological arousal occurred in most active conditions and for all physiological variables except cortisol. Playgroup leaders in daycare centers filled out a Swedish version of the scale measuring Type A behavior, and boys obtained significantly higher scores than girls. Whereas Type A scores were relatively consistent over time, however, physiological reactivity was not a stable individual characteristic, and correlations between Type A scores and cardiovascular reactivity reached significance in only 4 of 33 tests for the boys (one negative correlation) and in 1 case for the girls. Correlations between Type A scores and catecholamine reactivity did not reach significance. In summary, the data do not support the assumption of a consistent relationship between Type A behavior and physiological reactivity in preschool children. A significant correlation (r = .57, p less than .01) found for boys during a computer game suggests that an association may exist during "Type A-relevant" challenge.

Type A behaviour in pre-school children: interrater reliability, stability over six months and subcomponents.

Type A behaviour was measured in 250 boys and 245 girls (ages 3-7) using a Swedish version of Matthews' Youth Test for Health (MYTH). In addition, speech and voice characteristics (speed, loudness, response latency) were measured. Each child was independently rated by two play group leaders and measurements were repeated after a six month interval. Interrater reliability (first session) was 0.76 for both sexes and did not change with the age of the child. Boys obtained significantly (p less than 0.0001) higher scores than girls. Correlations over the six month period were 0.64 and 0.60 (p less than 0.001) for the two possible combinations of different raters and slightly higher (0.75 and 0.68, p less than 0.001) when the same rater was used. Two components of Type A behaviour were identified from a factor analysis of the data: impatience and competitiveness, and they accounted for 57% of the total variance. As for the total scale, boys obtained significantly higher scores than girls on both subscales. Scores on the competitiveness scale increased systematically with age. Speech and voice characteristics correlated significantly with Type A scores (total Type A behaviour: r = 0.50, using different raters, and 0.71, using the same raters, p less than 0.001) and, once again, boys obtained significantly (p less than 0.001) higher scores than girls. The results are in close agreement with the American findings from the original scale. It was concluded that the scale provides a reliable and valid instrument for measuring Type A or Type A-like behaviours in pre-school children.

Familial similarity in Type A behaviour and physiological measurements as related to sex.

Thirty-one families with pre-school children were examined with regard to Type A behaviour and cardiovascular and neuroendocrine measurements. Type A scores (MYTH) of the children from the ages of three to six were positively correlated with independent Type A measurements (Jenkins Activity Survey, Bortner Type A scale) of the parents (significant for fathers but not for mothers). The children's resting systolic blood pressures were significantly correlated with maternal and paternal values, while no significant familial aggregation was found for diastolic blood pressure, heart rate, catecholamine or cortisol excretion. The children's systolic and diastolic blood pressures and adrenaline excretion were significantly correlated between ages three and six. The results are consistent with the assumption that genetic as well as environmental factors contribute to the development of Type A behaviour. No significant association was found between Type A scores and physiological measurements during routine activities in the children or the adults.