Angela Iannitelli

SCHIZOPHRENIA AND NEUROGENESIS: A STEM CELL APPROACH

Several recent research findings indicate that schizophrenia (SCZ) may begin with an abnormal neuro-genesis from embryonic Neural Stem Cells (NSCs) and that this process may be particularly vulnerable to a number of genetic and/or environmental disturbances of early brain development. Since it is now well known that neurogenesis is not confined to the womb, but is a protracted process continuing in postnatal life well into adolescence and beyond, and since in the majority of subjects diagnosed with SCZ the first psychotic break occurs in late adolescence or early adulthood, the aim of our paper is to summarize the main findings supporting a possible link between changes in developmental postnatal neurogenesis and SCZ, with a specific focus on the critical period of adolescence and associated environmental risk factors. Establishing a significant role of adult neurogenesis in the emergence of psychosis will help us not only to better understand the pathogenesis of this neuopsychiatric disorder, but also to provide the key to potential strategies toward possible treatments and/or early corrective interventions.

Daily serum and salivary BDNF levels correlate with morning-evening personality type in women and are affected by light therapy

INTRODUCTION BDNF is present in human serum and its level changes have been used as a marker of antidepressant efficacy in some psychiatric disorders. In addition, the positive effects of light therapy on major depression suggest that circadian-regulated factors should be taken into account in the management of mood disorders. The aim of the present study was to test ultradian fluctuations in serum and salivary BDNF levels and their interaction with light therapy in a sample of healthy women. METHODS The study included 16 young women. Psychopathological status and chronotype traits were assessed by SPAQ, BDI, STAI, TAS, and MEQ. Standard light treatment protocol was applied. Serum and saliva were collected at 8.00, 13.00 and 20.00 hrs on the same day and at the end of light therapy. RESULTS BDNF levels declined over the course of the day both in serum and saliva, and a correlation between diurnal BDNF trend and personality traits and habits characterizing the morning and evening types in healthy women was found. CONCLUSIONS The present study is one of the first to show measurable BDNF in human saliva and to demonstrate its daily fluctuations in both saliva and serum of healthy young women. The correlation between diurnal changes in BDNF and the personality traits associated with body rhythms corroborates the notion that salivary BDNF may be a useful biomarker for stress-related research and different clinical investigations.

Spatial learning in men undergoing alcohol detoxification

Alcohol dependence is a major public health problem worldwide. Brain and behavioral disruptions including changes in cognitive abilities are common features of alcohol addiction. Thus, the present study was aimed to investigate spatial learning and memory in 29 alcoholic men undergoing alcohol detoxification by using a virtual Morris maze task. As age-matched controls we recruited 29 men among occasional drinkers without history of alcohol dependence and/or alcohol related diseases and with a negative blood alcohol level at the time of testing. We found that the responses to the virtual Morris maze are impaired in men undergoing alcohol detoxification. Notably they showed increased latencies in the first movement during the trials, increased latencies in retrieving the hidden platform and increased latencies in reaching the visible platform. These findings were associated with reduced swimming time in the target quadrant of the pool where the platform had been during the 4 hidden platform trials of the learning phase compared to controls. Such increasing latency responses may suggest motor control, attentional and motivational deficits due to alcohol detoxification.

Serum BDNF and NGF Modulation by Olive Polyphenols in Alcoholics duringWithdrawal

Many studies have suggested possible relationships between the neurotrophins brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) and alcohol addiction. Previous reports demonstrated severe changes in these neurotrophins in the serum of alcohol dependent patients and during withdrawal. Alcohol dependence syndromes during consumption and/or withdrawal are also characterized by elevated oxidative stress. Polyphenols, including olive polyphenols, are natural compounds known to possess marked antioxidant properties. Thus, this study was carried out in order to verify the effects of a blend of olive polyphenols supplementation containing mostly hydroxytyrosol (50 mg/day for 15 consecutive days) in alcoholic men during withdrawal on serum BDNF and NGF. As controls a group of alcohol dependent patients received sucrose tablets as placebo. BDNF and NGF were measured by ELISA on day 1, 3, 7 and 15 of the detoxification period. Some parameters of oxidative stress were analyzed too as free oxygen radicals defense (FORD) and free oxygen radicals test (FORT). No differences in oxidative status due to polyphenols were found. However, withdrawal elicited a mild increase in BDNF over two weeks that was counteracted on day 3 by polyphenols. As for NGF no effects of polyphenols supplementation were discovered to antagonize the expected NGF serum elevation during withdrawal. In conclusion the present data may indicate that monitoring serum BDNF and/or NGF in alcoholics undergoing detoxification could contribute to characterize alcohol dependence profiles to improve recovery processes throughout also antioxidant compounds.

Nerve growth factor, brain-derived neurotrophic factor, and the chronobiology of mood: a new insight into the "neurotrophic hypothesis"

The light information pathways and their relationship with the body rhythms have generated a new insight into the neurobiology and the neurobehavioral sciences, as well as into the clinical approaches to human diseases associated with disruption of circadian cycles. Light-based strategies and/or drugs acting on the circadian rhythms have widely been used in psychiatric patients characterized by mood-related disorders, but the timing and dosage use of the various treatments, although based on international guidelines, are mainly dependent on the psychiatric experiences. Further, many efforts have been made to identify biomarkers able to disclose the circadian-related aspect of diseases, and therefore serve as diagnostic, prognostic, and therapeutic tools in clinic to assess the different mood- related symptoms, including pain, fatigue, sleep disturbance, loss of interest or pleasure, appetite, psychomotor changes, and cognitive impairments. Among the endogenous factors suggested to be involved in mood regulation, the neurotrophins, nerve growth factor, and brain-derived neurotrophic factor show anatomical and functional link with the circadian system and mediate some of light-induced effects in brain. In addition, in humans, both nerve growth factor and brain-derived neurotrophic factor have showed a daily rhythm, which correlate with the morningness-eveningness dimensions, and are influenced by light, suggesting their potential role as biomarkers for chronotypes and/or chronotherapy. The evidences of the relationship between the diverse mood-related disorders, with a specific focus on depression, and neurotrophins are reviewed and discussed herein in terms of their circadian significance, and potential translation into clinical practice.

Seizure threshold variations in ECT-treated chronic patients with schizophrenia: a brief report

Seizure threshold (ST) is a parameter that differs in each person and can be modified both spontaneously and because of drug intake and/or other exogenous factors. A rise in ST during a course of electroconvulsive therapy (ECT) has been demonstrated in patients with depression and mania, but little information has been available as to whether the same result occurs in schizophrenia (SCZ). 11 male patients underwent estimation of the seizure threshold over a bilateral ECT course. Mean ST changed not significantly. No correlations were found between baseline ST and Positive and Negative Syndrome Scale (PANSS) scores. A significant positive correlation emerged between baseline ST and the variation of Hamilton Depression Rating Scale (HDRS) total and cognitive scores. The results suggest that ST in SCZ patients is not related to baseline psychopathological features, it is not related to clinical improvements of negative or positive SCZ symptoms and it does not change during the ECT course but it appears predictive of the improvement of affective and cognitive symptmos.

Immediate serum growth hormone decrease as a potential index of dopamine-related response to electroconvulsive therapy in schizophrenic patients.

Objectives: The objective of this study was to investigate the immediate response of the dopamine-regulated growth hormone (GH) to electroconvulsive therapy (ECT) in schizophrenic patients and the changes in the serum GH levels throughout the consecutive sessions of the therapeutic ECT course. Methods: Serum GH levels were measured in a sample of 11 men with schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, who were administered a course of 8 bilateral ECT treatments. Measurements were performed 5 minutes before ECT, during ECT, 15 minutes after an ECT session, and 30 minutes after an ECT session during the first, fourth, and eighth ECT sessions. Results: At both the fourth and the eighth ECT sessions, a significant decrease in GH levels 15 and 30 minutes after ECT was observed compared with the baseline values. No change in baseline serum GH levels was observed either during or at the end of the treatment. Clinical improvement was indicated by a significant reduction in the total score, negative subscale score, and positive subscale score of the Positive and Negative Syndrome Scale. Conclusions: The results are consistent with the potential role of immediate serum GH changes as an index of potential dopamine-mediated response to ECT. It can be assumed that GH reduction may be partially related to an antidopaminergic action of ECT, but further research is still needed to better evaluate the correlation of the dopamine system instability during the course of the illness with the previously mentioned immediate treatment response. Also, the role of other neurotransmitters in the regulation of GH production and ECT response must be taken into account for the purpose of an overall evaluation of the results and of their potential clinical implications.

Ocular Nerve Growth Factor (NGF) and NGF Eye Drop Application as Paradigms to Investigate NGF Neuroprotective and Reparative Actions

The eye is a central nervous system structure that is uniquely accessible to local treatment. Through the ocular surface, it is possible to access the retina, optic nerve, and brain. Animal models of retina degeneration or optic nerve crush could thus serve as tools to investigate whether and how factors, which are anterogradely or retrogradely transported through the optic nerve, might contribute to activate neuroprotection and eventually regeneration. Among these factors, nerve growth factor (NGF) plays a crucial role during development of the visual system, as well as during the entire life span, and in pathological conditions. The ability of NGF to exert survival and trophic actions on the retina and brain cells when applied intraocularly and topically as eye drops is critically reviewed here, together with the effects of ocular neurotrophins on neuronal pathways influencing body rhythm, cognitions, and behavioral functions. The latest data from animal models and humans are presented, and the mechanism of action of ocularly administered NGF is discussed. NGF eye drops are proposed as an experimental strategy to investigate the role and cellular targets of neurotrophins in the mechanism(s) underlying neurodegeneration/regeneration and their involvement in the regulation of neurological and behavioral dysfunctions.

[Omosexual parents: does a need exist for a reflection by mental health experts?].

The upbringing of children by couples of omosexual parents, both male and female, is a rapidly growing phenomenon in many countries, despite some differences due to variable national laws. In front of the numerical increase of new family typologies, their acceptance by the public opinion is very often a critical and this attitude is prevailingly shared also by the experts of mental health, such as psychologists and psychiatrists. Nevertheless, absolutely without any a priori prejudice, the absence of not yet available statistical data in large populations emphasizes the need to explore in depth the possible existence of specific psychological late consequences in young and adult age, in studies devoid of any cultural bias. Considering the children not as objects of the right of a couple to have sons, but as subjects of their own right to receive a well regulated and balanced affective and relational education should be a critical ethical issue.