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

Lithium from mood stabilizer to putative cognitive enhancer

This study is the first to have demonstrated, by means of a highly sensitive test of visual memory, a potential hippocampus neuroprotective effect of lithium in patients with BD. Undoubtedly, other studies are needed to finally recognize lithium as a potential cognitive enhancer. Future studies should include, apart from highly sensitive cognitive tests, specific neurotrophic biomarkers, such as BDNF, NGF, etc. Finally, it will be of outmost importance to evaluate the minimal length of treatment and the optimum serum level in order to combine potential clinical benefit and, particularly for older patients, clinical safety

Demographic variables, clinical aspects, and medicolegal implications in a population of patients with adjustment disorder

INTRODUCTION: Although adjustment disorder (AD) is considered as residual diagnosis and receives little attention in research, it plays an important role in clinical practice and also assumes an increasingly important role in the field of legal medicine, where the majority of diagnostic frameworks (eg, mobbing) often refer to AD. Our study aimed to look for specific stressor differences among demographic and clinical variables in a naturalistic setting of patients with AD. METHODS: A restrospective statistical analysis of the data of patients diagnosed with AD from November 2009 to September 2012, identified via manual search from the archive of the outpatient setting at the University Unit of Psychiatry "A. Fiorini" Hospital, Terracina (Latina, Italy), was performed. RESULTS: The sample consisted of 93 patients (46 males and 47 females), aged between 26 and 85, with medium-high educational level who were mainly employed. In most cases (54.80%), a diagnosis of AD with mixed anxiety and depressed mood was made. In all, 72% of the sample reported a negative family history for psychiatric disorders. In 22.60%, a previous history of psychopathology, especially mood disorders (76.19%), was reported. The main stressors linked to the development of AD were represented by working problems (32.30%), family problems (23.70%), and/or somatic disease (22.60%) with significant differences with respect to age and sex. Half of the patients were subjected to a single first examination; 24.47% requested a copy of medical records. CONCLUSION: Confirming previous data from previous reports, our results suggest that AD may have a distinct profile in demographic and clinical terms. Increased scientific attention is hoped, particularly focused on addressing a better definition of diagnostic criteria, whose correctness and accuracy are critical, especially in situations with medicolegal implications

Potential neuroprotective effect of lithium in bipolar patients evaluated by neuropsychological assessment. Preliminary results

OBJECTIVE: Accumulating evidence is delineating a neuroprotective/neurotrophic role for lithium. However, its primary effects on cognition remain ambiguous. We sought to investigate the profile of cognitive impairment in patients with bipolar disorder and to determine whether continued treatment with lithium preserves cognitive functioning. METHODS: In this cross-sectional study, we tested 15 euthymic patients with bipolar I disorder undergoing long-term clinical maintenance treatment with lithium (for at least 12 months), 15 matched patients treated with other mood-stabilizing drugs and who had never received lithium, and 15 matched healthy subjects on the Cambridge Neuropsychological Test Automated Battery. Investigated cognitive domains were visual memory, executive functions, attention, decision-making/impulsivity, and response inhibition. We controlled for age, gender, intelligence, and residual psychiatric symptomatology. RESULTS: Taken together, bipolar patients demonstrated robust deficits in visual memory and executive functions. Once subdivided in treatment subgroups, only non-lithium bipolar patients demonstrated impairments in visual memory. Attention, decision-making, and response inhibition were preserved in both groups. No correlation emerged between neuropsychological tests performance, clinical, and psychological variables. CONCLUSIONS: This study is the first to our knowledge to have demonstrated, by means of a highly sensitive test of visual memory, a potential hippocampus neuroprotective effect of lithium in patients with bipolar disorder. Besides, it confirms prior findings of cognitive deficits in euthymic bipolar patients

From Adolescent Neurogenesis to Schizophrenia: Opportunities, Challenges and Promising Interventions

Schizophrenia is a maldevelopmental disease with multifactorial etiopathogenesis linked to disturbances in the prenatal/ perinatal environment and to social factors and/or addictive drugs consumption during adolescence/young adulthood. Adolescence has been demonstrated to represent a very sensitive period for brain development. Exposure to adverse life events (chronic social isolation and/or instability) and/or addictive drugs (opioids, cocaine, cannabinoids, alcohol, nicotine) during adolescence has been linked to deviations in the normal neurodevelopment, producing a brain particularly at risk of mental diseases. Several psychopharmacological drugs and environmental factors have been reported to protect against the detrimental effect on neurogenesis caused by the aforementioned genetic and/or epigenetic vulnerabilities. Nerve growth factor (NGF) is one of the strongest stimuli of adult/adolescent neurogenesis and a promising neuromodulator to prevent and/or ameliorate the various behavioral and cognitive schizophrenic symptoms. Biomed Rev 2017; 28: 62-69.Key words: schizophrenia, neurodevelopment, adolescence, stem cells, adult neurogenesis, addictive drugs, life events, NG

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

Olfactory identification deficits and associated response inhibition in obsessive-compulsive disorder: On the scent of the orbitofronto-striatal model

Olfactory identification ability implicates the integrity of the orbitofrontal cortex (OFC). The fronto-striatal circuits including the OFC have been involved in the neuropathology of Obsessive Compulsive Disorder (OCD). However, only a few studies have examined olfactory function in patients with OCD. The Brief Smell Identification Test (B-SIT) and tests from the Cambridge Neuropsychological Automated Battery (CANTAB) were administered to 25 patients with OCD and to 21 healthy matched controls. OCD patients showed a significant impairment in olfactory identification ability as well as widely distributed cognitive deficits in visual memory, executive functions, attention. , and response inhibition. The degree of behavioural impairment on motor impulsivity (prolonged response inhibition Stop-Signal Reaction Time) strongly correlated with the B-SIT score. Our study is the first to indicate a shared OFC pathological neural substrate underlying olfactory identification impairment, impulsivity, and OCD. Deficits in visual memory, executive functions and attention further indicate that regions outside of the orbitofronto-striatal loop may be involved in this disorder. Such results may help delineate the clinical complexity of OCD and support more targeted investigations and interventions. In this regard, research on the potential diagnostic utility of olfactory identification deficits in the assessment of OCD would certainly be useful. © 2013 Elsevier Ireland Ltd

Cannabis use related to early psychotic onset. Role of premorbid function

The present cross-sectional study investigates the relation between Cannabis and the development of a psychotic disorder. The main objective is to explore the relations between Cannabis use and psychosis onset, premorbid adjustment cognitive impairment and familiarity. Forty-three patients with a diagnosis of Psychotic Disorder were recruited and divided in two groups based on Cannabis use before onset: Cannabis-using patients (PCU, N=21) and Cannabis-free patients (PCF, N=22). Cognitive functioning was evaluated by Trail Making Test A and B (TMT), Rey-Osterrieth Complex Figure Test (ROCF), and the Rey Auditory-Verbal Learning Test (RAVLT). Premorbid functioning was assessed retrospectively through the Premorbid Adjustment Scale (PAS). PCU group showed earlier onset of the psychotic disorder compared to PCF (p=0.008). This finding was not influenced by age or positive family history for psychiatric illness. PCU subjects showed a worse premorbid functioning respect to PCF and this difference was found to impact on the early onset in the PCU group. In conclusion the present study suggests the hypothesis of an interactive role of Cannabis and poor premorbid school adjustment in the development of psychotic disorders

Neurological soft signs and cerebral measurements investigated by means of MRI in schizophrenic patients

Neurophysiologic research has shown a Neurological Soft Sign (NSS) characteristic prevalence in schizophrenic patients, and correlations between NSS and the most frequently cerebral alterations. The aim of this study was to investigate, by means of MRI, the quantitative alterations of cortical and subcorticat structures and their correlation with NSS in a sample of schizophrenic patients. Linear measures of lateral ventricular (Evans ratio), third ventricular (Third Ventricular Width), hippocampal (Interuncal Index) and cerebellar (Verm Cerebellar Atrophy) atrophy were made on magnified MR images of 33 patients with a DSM IV diagnoses of chronic schizophrenia. NSS were evaluated with the Buchanan and Heinrichs's Neurological Evaluation Scale (NES). Lateral ventricular enlargement showed to be correlated with right stercoagnosia item (p = 0.001). Hippocampal atrophy, with right stereoagnosia item (p = 0.023), with forefinger-right thumb opposition (p = 0.004), forefinger-left thumb opposition (p = 0.029 and face-hand extinction (0.26). Third ventricle enlargement showed to be correlated with forefinger-right thumb opposition (p = 0.001), forefinger-left thumb opposition(p = 0.021) and total sensorial integration (p = 0.012). Cerebellar atrophy showed to be correlated with rhythmic drumming item (p = 0.042), forefinger-right thumb opposition (p = 0.007), forefinger-left thumb opposition (p = 0.026), left specular movements (p=0.049), face-hand extinction (p=0.001), right-left confusion (p=0.005) and with left forefinger-nose index (P=0.032). Results obtained confirm the correlation between NSS and neuroanatomical alterations in schizophrenia. (c) 2006 Published by Elsevier Ireland Ltd