Declarative Memory Impairment and Emotional Bias in Recurrent Depression with a Seasonal Pattern: The Interplay between Emotion and Cognition in Seasonal Affective Disorder.

Seasonal Affective Disorder (SAD) is a subtype of Major Depressive Disorder (MDD) with a seasonal pattern. Although it is a pathological condition limited to specific seasons of the year, during the symptomatic period, patients may experience a significant impairment of well-being and daily quality of life as a result of the depressed mood, associated with other symptoms defined as atypical of MDD. While extensive evidence of memory deficits has been found in MDD, explicit memory impairments in SAD are insufficiently studied. This study aims to investigate the cognitive processing of emotional stimuli in women with SAD, in particular the interplay between emotions and declarative memory. One hundred and twenty young women, screened from an initial number of 1125 university students, were divided into two groups, an experimental one that included 60 medically untreated women affected by "winter type SAD" and a control group of 60 non-SAD women. Different subjects were randomly submitted to two types of audio−visual stories, neutral or arousal, and then their memory performances were analyzed by means of a free-recall test and a recognition memory test. In both the free-recall test (p < 0.008) and in the recognition memory test (p < 0.002), the SAD group showed impaired memory performances. Taken together, our novel key findings suggest that SAD is characterized by impairment in declarative memory and attentional bias for emotional negative stimuli.

Gender differences in ultradian serum levels of NGF and BDNF correlate with psychophysical traits in healthy humans.

We aimed at investigating the gender and/or ultradian pattern of serum levels of the Nerve Growth Factor (NGF) and Brain-Derived Neurotrophic Factor (BDNF). Blood samples were collected at the 8.00, 13.00 and 20.00 hours of the day in healthy men and women, and the neurotrophins concentration was measured in the serum by ELISA. A further aim of the study was to evaluate whether or not the NGF/BDNF variations might be related to specific physiological or psychological traits as mood, feeling good and feeling rested, sexual desire and energy. Heart rate and blood pressure were also monitored at the same hours in each enrolled subject. The anxiety (STAI-T and STAI-S score) and sleeping quality were once evaluated in the morning too. We found that serum BDNF increases in men and decreases in women from morning to evening, while NGF shows a similar ultradian profile between men and women, but with higher concentrations in women. Both neurotrophins also show gender-related associations with psychophysiological variables. High NGF levels correlated with a high score for all the psychological variables in men, but with a low score in women. An inverse correlation was found between BDNF and energy and sexual desire in women, while no correlations were found in men. These data disclose that the condition of well-being (or activity/arousal status) is featured by an increasing NGF profile in men and a negative BDNF/NGF trend in women. The clinical relevance of the present data is discussed.

Assessment of premenstrual symptoms: validation of the Italian version of the Premenstrual Symptoms Screening Tool.

PURPOSE: The aim of this study was to provide an Italian validation of the Premenstrual Symptoms Screening Tool (PSST). The PSST is a retrospective questionnaire, originally developed in English language, used for the screening of Premenstrual Syndrome (PMS) and of Premenstrual Dysphoric Disorder (PMDD). PMDD and PMS are common, but are often not adequately recognized and treated, although they can heavily interfere on women's quality of life. METHODS: An Italian version of the PSST from English was prepared using the "forward-backward" procedure, and submitted to a sample of 520 women over 18 years of age (mean age of 23.6; DS=±3.1). The content validity, the internal consistency, the test-retest reliability, and the convergent validity were evaluated. The factorial structure underlying the questionnaire was assessed with the use of both Exploratory Factor Analysis (EFA) and Confirmatory Factor Analysis (CFA). RESULTS: Among the 520 participants to the study, 337 experienced no or mild premenstrual symptoms (64.8%), while 158 women evidenced a positive screening for moderate or severe PMS (30.4%), and 23 for PMDD (4.4%). The Italian PSST displayed adequate content validity and a very good internal consistency, with a Cronbach's alpha of 0.89. The test-retest reliability showed satisfactory results, with a Spearman's ρ for the overall score of 0.80, and the intra-class correlation coefficient (ICC) of 0.810 (95% CI=0.761-0.862; p<0.001). The EFA was performed using the principal component analysis, followed by varimax rotation. The CFA was conducted on EFA results and supported a four-factor model, yielding the best fit indices [χ2/df=1.76; CFI=0.920; TLI=0.904; RMSEA=0.054 (0.043-0.065)]. The convergent validity, evaluated using the Spearman's correlation coefficient between the overall score of the Italian version of PSST and the Beck Depression Inventory (BDI) score showed a good value (ρ=0.647 p<0.001). CONCLUSION: Our results support the cross-cultural validity of the questionnaire, suggesting that the Italian version is a reliable and valid tool, as well as easy to use, to screen women in need of treatment for their premenstrual symptoms.

Effects of sex steroid hormones on memory.

Many evidences have elucidated relevant mechanisms of action of estrogen, progesterone, and testosterone on cognition, including learning and memory processes, both in animal models and humans. This influence may depend on their modulator role on several neurotransmitter systems, and the extensive presence of their receptors in cerebral areas, involved in cognitive functions, including the amygdala, hippocampal formation, and cerebral cortex. The present brief review summarizes data of our research and others with the aim of clarifying, in mammals, the involvement of sex hormones on memory. In particular, after an introduction illustrating the general mechanisms of sex hormones modulation on memory processes, the specific role of estrogen, progesterone and testosterone in memory is described in three different sections. Besides summarizing the most relevant actions of sex steroid hormones in the modulation of learning and memory, in this review is also emphasized that many aspects and mechanisms are still not completely\r\nunderstood and extensive future research is necessary to elucidate them.

An instrument for the evaluation of muscle dysmorphia: The Italian validation of the adonis complex questionnaire.

BACKGROUND AND AIMS: Muscle dysmorphia (MDM), or bigorexia, is a subcategory of body dysmorphic disorder (BDD), also known as "Adonis Complex" in nonscientific contexts. One of the most used tools to investigate MDM is the Adonis Complex Questionnaire (ACQ). The ACQ is a 13-item US questionnaire, designed for male subjects only, related to the dissatisfaction and concerns about physical appearance. The aim of the current study was to evaluate the validity of the Italian version of the ACQ. METHODS: The instrument was administered to a sample of 322 male adults, recruited from the general population. We used the maximum-likelihood confirmatory factorial analysis (CFA), analyzing the covariance matrices with AMOS 24.0, to evaluate the different factorial models proposed in the literature. RESULTS: The evaluation of the factorial structure of the Italian version of the ACQ demonstrates the greater stability and internal consistency of the two-factor model, compared to the original three-factor model. The factors have no correlation with the demographic characteristics of the sample. CONCLUSIONS: The present study confirms the validity and the reliability of the Italian two-factor version of the ACQ and highlights the general tendency, among Italian males, to have concerns about their own physical appearance with recurring thoughts and eating behaviors finalized to improve it. Our study represents an advance in the use of adequate and reliable instruments to assess concerns about physical appearance in the Italian male population.

Night Eating Syndrome, circadian rhythms and seasonality: a study in a population of Italian university students.

PURPOSE: The aim of this research was to assess the prevalence of Night Eating Syndrome (NES) in a university student population and to clear up the relationship between NES, depression and chronotype. The relation between NES and seasonality was also investigated. METHODS: The data were collected from a sample of 1136 students of the L'Aquila University, Italy. All subjects were invited to answer to the Sociodemographic Information Form and to take a self-report battery composed by four questionnaires: the Night Eating Questionnaire (NEQ), the Morningness Eveningness Questionnaire (MEQ), the Seasonal Pattern Assessment Questionnaire (SPAQ) and the Beck Depression Inventory (BDI). RESULTS: The 5.3% of our population (60 subjects) reached the criteria for NES. The distribution of chronotypes in the sample was: Morning Type 15.3%, Intermediate 64.3% and Evening Type 20.4%. The 36.7% of the participants reaching the criteria for NES, obtained low scores on the MEQ. The data indicated that NEQ and MEQ scores are significantly inversely correlated (r=-.22; p<.01, two-tailed test). The 3.6% of our population (41 subjects) reached the criteria for Seasonal Affective Disorder (SAD) and 10.7% for subclinical SAD (121 subjects). Furthermore, the 11.7% of subjects with NES presented SAD and the 5% presented Subclinical SAD. The data demonstrated that NES and Global Seasonality Score (GSS) are significantly associated (r=.22; p<0.01, two-tailed test). CONCLUSIONS: The main finding of this study is the strong relation between NES and eveningness dimension. Our results help to clear up the literature debate about the role of eveningness dimension in the night eating, suggesting that subjects with NES present a circadian delay, not only in the food intake, but in the entire functioning. At the best of one knowledge this study is the first one to examine the relationship between NES and seasonality. This research found preliminary evidence that, similarly to the findings of previous studies in subjects with Bulimia Nervosa (BN) and Binge Eating Disorder (BED), night eating symptoms may vary significantly across the seasons; subjects with NES experience seasonal variation in their mood and in their eating patterns.

Electrophysiological and Behavioral Indices of the Role of Estrogens on Memory Processes for Emotional Faces in Healthy Young Women.

It is well known that estrogens influence cognitive activities, such as memory, and emotional states. The objective of the present study was to investigate the role of estrogens in the short-term memory processing of basic emotional face expressions, by means of event-related potentials (ERPs) and a recognition memory (RM) behavioral task. Healthy young women were divided into a periovulatory (PO) group, characterized by high levels of estrogens and low levels of progesterone, and an early follicular (EF) group, characterized by low levels of both estrogens and progesterone. During the RM task, all subjects viewed images of faces expressing six basic emotions (happiness, anger, disgust, sadness, surprise, fear) and one neutral expression while their electrophysiological activity was recorded. We considered P300 components, amplitude, and latency in response to each stimulus. Soon after the presentation of each stimulus face, a target image was presented, consisting of two faces, one of which was the same, while the other was a chimerical face, obtained by mixing the upper or lower halves of the faces of the stimulus image with a different emotion. The subjects had to choose between the two alternatives, and the reaction time (RT) and accuracy of response (RM errors) were measured. The main findings of this study showed that P300 amplitudes are significantly higher in response to the expressions of happiness, but significantly lower for sadness, in PO compared to EF. The P300 data are consistent with performance in the RM task and with the measures of RT. The interest in the emotion of happiness, unlike sadness, during the PO phase may reflect the evolutionary significance of female sex hormones linked to mating behavior.

The relationship between Night Eating Syndrome, depression and chronotype in a non-clinical adolescent population.

PURPOSE: The aim of the current study was to assess the prevalence of Night Eating Syndrome (NES) in a population of non-clinical adolescents and to investigate the relationship between NES, depression and eveningness dimension. METHODS: The data were collected from a sample of 301 subjects, 181 females and 120 males, aged between 15 and 19 (mean value 17.64, SD=1.3). All subjects were invited to answer demographic questions and to take a self-report battery composed by three questionnaires: the Night Eating Questionnaire (NEQ), the Morningness Eveningness Questionnaire (MEQ) and the Beck Depression Inventory (BDI). RESULTS: The distribution of chronotypes in the sample was: morning type 9%, intermediate 68.4% and evening type 22.6%. 4% of the participants (12 subjects) reached the criteria for NES. The data indicate that MEQ and NEQ scores are significantly inversely correlated (r=-0.157; p<0.01); 58.3% of the participants who reached the criteria for NES received low scores on the MEQ. The BDI scores resulted significantly associated with the NEQ variable (r=0.275; p=0.001). CONCLUSIONS: This is the first study, as far as we are aware, which has investigated the relationship between chronotype, depression and NES in an adolescent non-clinical population. The findings of our study highlight the high prevalence of NES in the adolescent population and indicate a significant association between eveningness dimension, Depression and NES.

Evidence of estrogen modulation on memory processes for emotional content in healthy young women.

PURPOSE: It is well accepted that emotional content can affect memory, interacting with the encoding and consolidation processes. The aim of the present study was to verify the effects of estrogens in the interplay of cognition and emotion. METHODS: Images from the International Affective Pictures System, based on valence (pleasant, unpleasant and neutral), maintaining arousal constant, were viewed passively by two groups of young women in different cycle phases: a periovulatory group (PO), characterized by high level of estrogens and low level of progesterone, and an early follicular group (EF), characterized by low levels of both estrogens and progesterone. The electrophysiological responses to images were measured, and P300 peak was considered. One week later, long-term memory was tested by means of free recall. FINDINGS: Intra-group analysis displayed that PO woman had significantly better memory for positive images, while EF women showed significantly better memory for negative images. The comparison between groups revealed that women in the PO phase had better memory performance for positive pictures than women in the EF phase, while no significant differences were found for negative and neutral pictures. According to the free recall results, the subjects in the PO group showed greater P300 amplitude, and shorter latency, for pleasant images compared with women in the EF group. CONCLUSION: Our results showed that the physiological hormonal fluctuation of estrogens during the menstrual cycle can influence memory, at the time of encoding, during the processing of emotional information.

When chocolate seeking becomes compulsion: gene-environment interplay.

BACKGROUND: Eating disorders appear to be caused by a complex interaction between environmental and genetic factors, and compulsive eating in response to adverse circumstances characterizes many eating disorders. MATERIALS AND METHODS: We compared compulsion-like eating in the form of conditioned suppression of palatable food-seeking in adverse situations in stressed C57BL/6J and DBA/2J mice, two well-characterized inbred strains, to determine the influence of gene-environment interplay on this behavioral phenotype. Moreover, we tested the hypothesis that low accumbal D2 receptor (R) availability is a genetic risk factor of food compulsion-like behavior and that environmental conditions that induce compulsive eating alter D2R expression in the striatum. To this end, we measured D1R and D2R expression in the striatum and D1R, D2R and α1R levels in the medial prefrontal cortex, respectively, by western blot. RESULTS: Exposure to environmental conditions induces compulsion-like eating behavior, depending on genetic background. This behavioral pattern is linked to decreased availability of accumbal D2R. Moreover, exposure to certain environmental conditions upregulates D2R and downregulates α1R in the striatum and medial prefrontal cortex, respectively, of compulsive animals. These findings confirm the function of gene-environment interplay in the manifestation of compulsive eating and support the hypothesis that low accumbal D2R availability is a "constitutive" genetic risk factor for compulsion-like eating behavior. Finally, D2R upregulation and α1R downregulation in the striatum and medial prefrontal cortex, respectively, are potential neuroadaptive responses that parallel the shift from motivated to compulsive eating.

Zaprinast impairs spatial memory by increasing PDE5 expression in the rat hippocampus.

In this work, we report the effect of post-training intraperitoneal administration of zaprinast on rat memory retention in the Morris water maze task that revealed a significant memory impairment at the intermediate dose of 10mg/kg. Zaprinast is capable of inhibiting both striatal and hippocampal PDE activity but to a different extent which is probably due to the different PDE isoforms expressed in these areas. To assess the possible involvement of cyclic nucleotides in rat memory impairment, we compared the effects obtained 30 min after the zaprinast injection with respect to 24h after injection by measuring both cyclic nucleotide levels and PDE activity. As expected, 30 min after the zaprinast administration, we observed an increase of cyclic nucleotides, which returned to a basal level within 24h, with the exception of the hippocampal cGMP which was significantly decreased at the dose of 10mg/kg of zaprinast. This increase in the hippocampal region is the result of a cGMP-specific PDE5 induction, confirmed by sildenafil inhibition, in agreement with literature data that demonstrate transcriptional regulation of PDE5 by cAMP/cGMP intracellular levels. Our results highlight the possible rebound effect of PDE inhibitors.

Habit learning and memory in mammals: behavioral and neural characteristics.

Goal-direct behavior and habit learning represent two forms of instrumental learning; whereas the former is rapidly acquired and regulated by its outcome, the latter is reflexive, elicited by antecedent stimuli rather than their consequences. Habit learning can be generally defined as the acquisition of associations between stimuli and responses. Habits are acquired via experience-dependent plasticity, occurring repeatedly over the course of days or years and becoming remarkably fixed. The distinction between habit learning, as a product of a procedural learning brain system, and a declarative learning system for encoding facts and episodes is based on the hypothesis that memory is composed of multiple systems that have distinct neuroanatomy and operating principles. Here we review recent research analyzing the main behavioral and neural characteristics of habit learning. In particular, we focus on the distinction between goal-directed and habitual behavior, and describe the brain areas and neurotransmitters systems involved in habit learning. The emotional modulation of habit learning in rodents and primates is reviewed, and the implications of habit learning in psychopathology are briefly described.

Serotonergic 5-HT7 receptors and cognition.

The abundant distribution of serotonin (5-HT) in different areas of the central nervous system can explain the involvement of this neurotransmitter in the regulation of several functions, such as sleep, pain, feeding, and sexual and emotional behaviors. Moreover, the serotonergic system is also involved in other more complex roles, such as cognition, including learning and memory processes. Recent studies led to the discovery of various types and subtypes of receptors differentially associated to cognitive mechanisms. 5-HT7 is the most recently discovered receptor for 5-HT; therefore, it is also one of the least well characterized. Studies exist hypothesizing the role of 5-HT7 on the modulation of learning and memory processes and other cognitive functions. Moreover, much attention has been devoted to the possible role of 5-HT7 receptors in psychiatric disorders. Therefore, the aim of this review is to clarify the behavioral role of the recently discovered 5-HT7 type receptor and highlight its involvement in the cognitive functions, with particular attention to the modulation of learning and memory processes, thus providing a basis to obtain new therapeutic agents and strategies for the treatment of cognitive disorders.

Estrogen, cognitive functions and emotion: an overview on humans, non-human primates and rodents in reproductive years.

Accumulating evidence has highlighted a number of important, global issues regarding the influence of estrogen on emotion and cognitive functions,including learning and memory processes, both in animal models and humans. The influence of estrogen on cognition and emotion can be explained by taking into account its modulator role on several neurotransmitter systems, acetylcholine in particular, but also catecholamines,serotonin and GABA in rodents, primates and humans. Another reason may lie in the wide spread presence of the two classes (a and~) of estrogen receptors in many brain regions involved in emotion and cognition, including the hippocampal formation, amygdala and cerebral cortex. The present review reports on research conducted in our laboratory and others with the objective of identifying the action of estrogens on cognition and emotion in rodents, monkeys and humans in youth. In particular, the first section,focused on the mechanisms of estrogens action in the brain, illustrates the involvement of estrogen receptors and neurotransmitters in the cognitive and emotional processes; the second section deals with the estrogen effects on cognitive and emotional mechanisms, with particular emphasis on memory and the involvement of estrogen in emotion and cognition across the estrous/menstrual cycle.

Estrogens and memory in physiological and neuropathological conditions.

Ovarian hormones can influence brain regions crucial to higher cognitive functions, such as learning and memory, acting at structural, cellular and functional levels, and modulating neurotransmitter systems. Among the main effects of estrogens, the protective role that they may play against the deterioration of cognitive functions occurring with normal aging is of essential importance. In fact, during the last century, there has been a 30 years increase in female life expectancy, from 50 to 83 years; however, the mean age of spontaneous menopause remains stable, 50-51 years, with variability related to race and ethnicity. Therefore, women are now spending a greater fraction of their lives in a hypoestrogenic state. Although many cognitive functions seem to be unaffected by normal aging, age-related impairments are particularly evident in tasks involving working memory (WM), whose deficits are a recognized feature of Alzheimer's disease (AD). Many studies conducted over the past two decades showed that the female gonadal hormone estradiol can influence performance of learning and memory tasks, both in animal and humans. There is a great deal of evidence, mostly from animal models, that estrogens can facilitate or enhance performance on WM tasks; therefore, it is very important to clarify their role on this type of memory. To this aim, in this review we briefly describe the most relevant neurobiological bases of estrogens, that can explain their effects on cognitive functioning, and then we summarize the results of works conducted in our laboratory, both on animals and humans, utilizing the menstrual/estrous cycle as a useful noninvasive model. Finally, we review the possible role of estrogens in neuropathological conditions, such as AD and schizophrenia.

Sex-related memory recall and talkativeness for emotional stimuli.

Recent studies have evidenced an increasing interest in sex-related brain mechanisms and cerebral lateralization subserving emotional memory, language processing, and conversational behavior. We used event-related-potentials (ERP) to examine the influence of sex and hemisphere on brain responses to emotional stimuli. Given that the P300 component of ERP is considered a cognitive neuroelectric phenomenon, we compared left and right hemisphere P300 responses to emotional stimuli in men and women. As indexed by both amplitude and latency measures, emotional stimuli elicited more robust P300 effects in the left hemisphere in women than in men, while a stronger P300 component was elicited in the right hemisphere in men compared to women. Our findings show that the variables of sex and hemisphere interacted significantly to influence the strength of the P300 component to the emotional stimuli. Emotional stimuli were also best recalled when given a long-term, incidental memory test, a fact potentially related to the differential P300 waves at encoding. Moreover, taking into account the sex-related differences in language processing and conversational behavior, in the present study we evaluated possible talkativeness differences between the two genders in the recollection of emotional stimuli. Our data showed that women used a higher number of words, compared to men, to describe both arousal and neutral stories. Moreover, the present results support the view that sex differences in lateralization may not be a general feature of language processing but may be related to the specific condition, such as the emotional content of stimuli.

Working and reference memory across the estrous cycle of rat: a long-term study in gonadally intact females.

The results of many studies conducted over the past two decades suggested a role of estrogen on mammal's ability to learn and remember. In the present paper, we analyzed the influence that the endogenous fluctuation of estrogen, naturally present across the different phases of estrous cycle of female rats, can exert over the performance of tasks utilized to assess memory. In particular, we analyzed the performances in an eight arms radial maze task, dependent upon working memory, and in a water maze (WM) task, dependent upon spatial reference memory. The water maze is aversively motivated by the desire to escape onto a safe platform, whereas the radial arm maze (RAM) is motivated by food reward. The difference in reinforcement may affect the speed of learning, the strategy adopted and the necessity for accurate navigation. Therefore, coherent results obtained through the two different tasks can be due to mnemonic factors. The study was conducted during a long period of time, 14 months, utilizing gonadally intact females, without pharmacological and surgical treatments. In order to evaluate the post-acquisition phase we first trained the animals to reach the criterion in performing tasks, and then we submitted them to experimental phase. Our results show that estrogen can have an effect on memory processes, and that this effect may be different in relation to different kinds of memory. In fact, in our study, estrogen selectively improved working memory, but not reference memory, during post-acquisition performance of a RAM task with four baited and four un-baited arms. Moreover, WM performances showed that estrogen have a negative effect on spatial reference memory.

Estrogen and cognitive functions.

Although the effects of estrogen on sexual behavior in mammals are well known, its role on other types of behavior, including cognition, have only recently been recognized. This review summarizes work conducted in our laboratory and others with the aim of identifying the effects of estrogen on cognitive functions. The first section will briefly describe the neurobiology of estrogen. The second section will discuss the effects of estrogen on cognitive behaviors in mammals, as well as the physiological relevance of these effects and their applicability to human health and disease. The third section will detail the role of estrogen on working memory in humans and nonhuman primates, and in rodents. Finally, the concluding section will briefly describe the relationship between estrogen and the aging brain.

Working memory for emotional facial expressions: role of estrogen in humans and non-human primates.

In recent years, numerous studies focusing on the role of sex steroid hormones on neuropsychological functions have been reported. The influence of estrogens on cognition can be explained by the widespread presence of estrogen receptors (ERs) in limbic and cortical areas, and the modulator role of estrogens on numerous neurotransmitter systems. There is a great deal of evidence suggesting that estrogen can enhance memory processes and improve performance in working memory (WM) tasks, including face-tasks, delayed matching-to-sample (DMTS) and delayed non-matching-to-sample (DNMTS). The modulator effects exerted by estrogens are complex and may vary according to task, gender, and phase of the menstrual cycle. For many years, physiological hormonal fluctuations during the menstrual cycle, postpartum, and menopause have been said to influence mood, cognition, and affective disorders. In addition, it has been hypothesised that estrogens have a protective role in schizophrenia and Alzheimer's disease (AD). Taking into account that women's performance in memory tasks can also fluctuate with circulating hormone levels across the menstrual cycle, data related to the cognitive performance in a WM task for emotional facial expressions were reported. The findings described in this review can contribute to clarifying the role of the steroid hormone estrogen in the modulation of cognitive functions, particularly memory, and indicate the possible usefulness of applying a new paradigm, employing a DNMTS task with emotional facial expressions, in studies focused on emotional WM in relevant models of nonhuman primates. Such data could also represent a useful tool in individualizing effective therapy for the treatment of disturbances linked to menstrual cycle phases and menopause in women.