Aberrant cerebello-cerebral connectivity in remitted bipolar patients 1 and 2: new insight into understanding the cerebellar role in mania and hypomania

Objectives. Bipolar Disorder (BD) is a major mental illness characterized by periods of (hypo) mania and depression with inter-episode remission periods. Functional studies in BD have consistently implicated a set of linked cortical and subcortical limbic regions in the pathophysiology of the disorder, also including the cerebellum. However, the cerebellar role in the neurobiology of BD still needs to be clarified. Methods. Seventeen euthymic patients with BD type1 (BD1) (mean age/SD: 38.64/13.48; M/F:9/8) and 13 euthymic patients with BD type 2 (BD2) (mean age/SD: 41.42/14.38; M/F:6/7) were compared with 37 sex- and age-matched healthy subjects (HS) (mean age/SD: 45.65/14.15; M/F:15/22). T1 weighted and resting-state functional connectivity (FC) scans were acquired. The left and right dentate nucleus were used as seed regions for the seed based analysis. FC between each seed and the rest of the brain was compared between patients and HS. Correlations between altered cerebello-cerebral connectivity and clinical scores were then investigated. Results. Different patterns of altered dentate-cerebral connectivity were found in BD1 and BD2. Overall, impaired dentate-cerebral connectivity involved regions of the anterior limbic network specifically related to the (hypo)manic states of BD Conclusion. Cerebello-cerebral connectivity is altered in BD1 and BD2. Interestingly, the fact that these altered FC patterns persist during euthymia, supports the hypothesis that cerebello-cerebral FC changes reflect the neural correlate of subthreshold symptoms, as trait-based pathophysiology and/or compensatory mechanism to maintain a state of euthymia

Pharmacological Management of Anxiety Disorders in the Elderly

Anxiety disorders are common in the elderly. Additionally, anxiety symptoms often accompany co-morbid psychiatric, medical, as well as neurodegenerative diseases in the older population. Anxiety in the elderly, often accompanied by depression, can lead to worsening physical, cognitive and functional impairments in this vulnerable population. Antidepressants are considered first line treatment. Both SSRIs and SNRIs are efficacious and well-tolerated in the elderly. Some SSRIs are strong inhibitors of the cytochrome P450 hepatic pathway whereas others have less potential for drug interaction. Those antidepressants with more favorable pharmacokinetic profiles should be considered first-line in the treatment of anxiety. Mirtazapine and vortioxetine are also considered safe treatment options. Buspirone may have benefit, but lacks studies in elderly populations. Although tricyclic/tetracyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs) may be effective in the elderly, their side effect and safety profiles are suboptimal and thus are not recommended in late-life. Benzodiazepines and beta blockers should generally be avoided when treating anxiety in the elderly. There is not enough evidence to support the use of antipsychotics or mood stabilizers given their risk of problems in both the long and short term. In addition, antipsychotics have a black box warning for increased mortality in elderly patients with dementia

Anti-purkinje cell and natural autoantibodies in a group of psychiatric patients. Evidences for a correlation with the psychopathological status.

Phenomena of autoimmunity are frequent among psychiatric patients, but we don't know yet if they should be considered primary and linked to the pathophisiology of the disorder, or aspecific and associated to a general immune system activation. Paraneoplastic Cerebellar Degeneration (PCD) represents a well known model of specific autoimmunity. In order to better understand the abovementioned issues, we used this condition to compare a set of immune dysfunctions found in a group of psychiatric patients. For this reason we tested sera from 48 psychiatric patients (24 schizophrenics, 17 bipolars and 7 obsessive-compulsive), 22 PCD patients and 52 healthy controls for the presence of anti-Purkinje autoantibodies and of some natural autoantibodies (ANAs, AMAs, APCAs, ASMAs). Psychopatological status of the psychiatric patients was assessed with BPRS, SANS, SAPS, HAM-D, CGI-S. In the psychiatric group anti-Purkinje autoantibodies were identified in 11/48 (22,9%) patients, while they were present in 22/22 (100%) PCD patients and in 0/52 (0%) healthy controls. Among all anti-Purkinje autoantibody positive patients (in the PCD and psychiatric samples), only those belonging to the psychiatric sample, but not those with PCD, were frequently found positive also for natural autoantibodies, that are considered good markers of aspecific immune activation. In these patients, both anti-Purkinje and natural autoantibodies were found associated with acute/positive psychopathological symptoms. These results seem to point out that some phenomena of auto-immunity described in psychiatric patients could be aspecific, unrelated to the pathophysiology of the concomitant mental disorders and could be more frequent during phases of acute/positive symptoms