Kokras N, Dalla C.
Sex differences in animal models of psychiatric disorders. Br J Pharmacol 2014;171:4595-619.
AbstractPsychiatric disorders are characterized by sex differences in their prevalence, symptomatology and treatment response. Animal models have been widely employed for the investigation of the neurobiology of such disorders and the discovery of new treatments. However, mostly male animals have been used in preclinical pharmacological studies. In this review, we highlight the need for the inclusion of both male and female animals in experimental studies aiming at gender-oriented prevention, diagnosis and treatment of psychiatric disorders. We present behavioural findings on sex differences from animal models of depression, anxiety, post-traumatic stress disorder, substance-related disorders, obsessive-compulsive disorder, schizophrenia, bipolar disorder and autism. Moreover, when available, we include studies conducted across different stages of the oestrous cycle. By inspection of the relevant literature, it is obvious that robust sex differences exist in models of all psychiatric disorders. However, many times results are conflicting, and no clear conclusion regarding the direction of sex differences and the effect of the oestrous cycle is drawn. Moreover, there is a lack of considerable amount of studies using psychiatric drugs in both male and female animals, in order to evaluate the differential response between the two sexes. Notably, while in most cases animal models successfully mimic drug response in both sexes, test parameters and treatment-sensitive behavioural indices are not always the same for male and female rodents. Thus, there is an increasing need to validate animal models for both sexes and use standard procedures across different laboratories.
Kokras N, Papadopoulos L, Zervas IM, Spyropoulou A, Stamatelopoulos K, Rizos D, Creatsa M, Augoulea A, Papadimitriou GN, Lambrinoudaki I.
Psychological but not vasomotor symptoms are associated with temperament and character traits. Climacteric 2014;17:500-9.
AbstractOBJECTIVE: Recent evidence suggests that climacteric symptoms may be intensified by specific temperament and personality traits in postmenopausal women. In this study we investigate Cloninger's model of personality in relation to menopausal symptoms. METHODS: One-hundred and seventy peri- and postmenopausal women consecutively recruited from a menopause clinic of an academic hospital completed the Cloninger's Temperament and Character Inventory (TCI-140) which measures four dimensions of temperament: Harm avoidance, Novelty seeking, Reward dependence and Persistence, as well as three dimensions of character: Self-directedness, Cooperativeness, and Self-transcendence. Menopausal somatic, vasomotor and psychological symptoms were also assessed using the Greene Climacteric Scale. RESULTS: In comparison to the norms of the Greek general population, postmenopausal women presented lower scores in Novelty seeking and Reward dependence and higher scores in Persistence, Self-directedness, Cooperativeness and Self-transcendence. Higher harm avoidance (the inclination to avoid potential punishment, be shy and fearful of uncertainty) significantly correlated with anxiety and depressive symptoms while lower Self-directedness (the ability to have the willpower to adapt to or overcome any changes) correlated with depressive symptoms only. By multivariate regression analysis, higher Harm avoidance and lower Self-directedness were independently associated with the presence of depressive symptoms. No significant associations were observed between TCI-140 traits and somatic or vasomotor symptoms. CONCLUSIONS: Our findings indicate that most temperament and character traits according to Cloninger's model in peri- and postmenopausal women varied significantly as compared to the general population. Among several traits, high Harm avoidance and low Self-directedness were most strongly associated with psychological climacteric distress but not with somatic and vasomotor symptoms.
Kokras N, Pastromas N, Porto TH, Kafetzopoulos V, Mavridis T, Dalla C.
Acute but not sustained aromatase inhibition displays antidepressant properties. Int J Neuropsychopharmacol 2014;17:1307-13.
AbstractAromatase inhibitors block the conversion of androgens to oestrogens and are used for the treatment of hormone-responsive breast cancer in menopause and recently also in premenopausal women. We investigate whether decreased oestrogen synthesis following aromatase inhibition leads to a depressive-like behavioural response in cycling female rats. Using the forced swim test (FST) we estimate the response of acute (three injections in 24 h) and sustained (7 d) letrozole and fluoxetine administration. Acute aromatase inhibition decreases immobility duration in the FST, indicating its antidepressant potential. Instead, sustained aromatase inhibition did not show such antidepressant potential. Testosterone elevation associates with the decreased depressive behaviour in the FST following acute letrozole treatment, but interestingly progesterone explains the increased swimming behaviour. Present findings may have potential implications for women treated with aromatase inhibitors, especially before menopause, as well as for the role of gonadal hormones in the expression of depressive symptoms and antidepressant response.
Paparrigopoulos T, Melissaki A, Tzavellas E, Karaiskos D, Ilias I, Kokras N.
Increased co-morbidity of depression and post-traumatic stress disorder symptoms and common risk factors in intensive care unit survivors: a two-year follow-up study. Int J Psychiatry Clin Practice 2014;18:25-31.
AbstractOBJECTIVE: To investigate the long-term psychological impact of intensive care unit (ICU) hospitalization, as well as to establish risk factors which successfully discriminate patients at higher risk. METHODS: The Medical Outcomes Study Short Form Survey (SF-36), the Center for Epidemiologic Studies for Depression (CES-D), and the Davidson Trauma Scale (DTS) questionnaires were obtained from 48 ICU survivors who were also interviewed and self-reported on several acknowledged risk factors. RESULTS: A high co-morbidity between depression and post-traumatic stress disorder (PTSD) cases was observed. Both CES-D and DTS scores correlated negatively with the SF-36 mental health subscale scores; although a causative relation cannot be attributed to this finding, it indicates a potential negative impact of depression and PTSD symptoms on the patients' quality of life even at 18- to 24-month post-ICU. The most important risk factor associated with a long-term impact on quality of life, depression and PTSD was lifetime history of any psychiatric disorder. CONCLUSIONS: During ICU admissions efforts should be made towards identifying and psychologically supporting those patients with a previous history of a psychiatric disease, as they are at considerably higher risk of suffering from the long-term psychological sequelae of ICU admission.