Differential diagnoses and management strategies in patients with schizophrenia and bipolar disorder

Successful treatment of psychiatric disorders, including bipolar disorder and schizophrenia, is complicated and is affected by a broad range of factors associated with the diagnosis, choice of treatment and social factors. In these patients, treatment management must focus on accurate and early diagnosis, to ensure that correct treatment is administered as soon as possible. In both disorders, the treatment of the disease in the acute phase must be maintained long term to provide continuous relief and normal function; the treatment choice in the early stages of the disease may impact on long-term outcomes. In schizophrenia, treatment non-compliance is an important issue, with up to 50% of patients discontinuing treatment for reasons as diverse as efficacy failure, social barriers, and more commonly, adverse events. Treatment non-compliance also remains an issue in bipolar disorder, as tolerability of mood stabilizers, especially lithium, is not always good, and combination treatments are frequent. In order to achieve an optimal outcome in which the patient continues with their medication life-long, treatment should be tailored to each individual, taking into account treatment and family history, and balancing efficacy with tolerability to maximize patient benefit and minimize the risk of discontinuation. These case studies illustrate how treatment should be monitored, tailored and often changed over time to meet these needs

Assessing Working Memory via N-Back Task in Euthymic Bipolar I Disorder Patients: A Review of Functional Magnetic Resonance Imaging Studies

Bipolar disorder (BD) is a chronic and highly disabling mood disorder, associated with the highest suicide rate among psychiatric disorders. Even though neurobiological bases of BD have still to be further elucidated, recent neuroimaging studies provided compelling evidence about functional correlates of cognitive deficits in BD patients, with working memory (WM) impairment being one of the most commonly reported findings. Such dysfunctions are likely to persist beyond acute phases of the illness, so they qualify as endophenotypic markers for the disorder. This review sought to synthesize, through a MEDLINE search up to December 2012, published functional magnetic resonance imaging (fMRI) studies on WM networks, conducted through N-back task in euthymic BD I patients and including a control comparison group. Eight studies meeting the search criteria were identified. Despite heterogeneity across findings, particularly in relation to task performance (i.e. accuracy and reaction time), most studies reported a loss of connectivity in BD patients' prefrontal networks, traditionally involved in WM, as well as patterns of abnormal activation in the dorso/ventrolateral prefrontal cortex, other prefrontal areas and the parietal and temporal cortex. These findings suggest the involvement of intact secondary systems in order to overcome lack of integrity across WM circuits in BD patients. Further investigation in the field is warranted

The second AT-hook of the architectural transcription factor HMGA2 is determinant for nuclear localization and function

High Mobility Group A (HMGA) is a family of architectural nuclear factors which play an important role in neoplastic transformation. HMGA proteins are multifunctional factors that associate both with DNA and nuclear proteins that have been involved in several nuclear processes including transcription. HMGA localization is exclusively nuclear but, to date, the mechanism of nuclear import for these proteins remains unknown. Here, we report the identification and characterization of a nuclear localization signal (NLS) for HMGA2, a member of the HMGA family. The NLS overlaps with the second of the three AT-hooks, the DNA-binding domains characteristic for this group of proteins. The functionality of this NLS was demonstrated by its ability to target a heterologous β-galactosidase/green fluorescent protein fusion protein to the nucleus. Mutations to alanine of basic residues within the second AT-hook resulted in inhibition of HMGA2 nuclear localization and impairment of its function in activating the cyclin A promoter. In addition, HMGA2 was shown to directly interact with the nuclear import receptor importin-α2 via the second AT-hook. HMGA proteins are overexpressed and rearranged in a variety of tumors; our findings can thus help elucidating their role in neoplastic transformation

Clinical characteristics and long-term response to mood stabilizers in patients with bipolar disorder and different age at onset

INTRODUCTION : bipolar disorder (BD) is a prevalent, comorbid, and impairing condition. Potential predictors of response to pharmacological treatment are object of continuous investigation in patients with BD. The present naturalistic study was aimed to assess clinical features and long-term response to mood stabilizers in a sample of bipolar subjects with different ages at onset METHODS : the study sample included 108 euthymic patients, diagnosed as affected by BD, either type I or II, according to the DSM-IV-TR, who were started on mood stabilizer treatment. Patients were followed-up for 24 months and the occurrence of any mood episode collected. At the end of the follow-up, patients were divided in 3 subgroups according to the age at onset (early-onset 30-45 years, respectively) and the long-term response to mood stabilizers was compared between them along with other clinical features RESULTS : the three subgroups showed significant differences in terms of clinical and demographic features and, with respect to long-term response to mood stabilizers, the early-onset subgroup showed a better outcome in terms of reduction of major depressive episodes during the 24-month follow-up compared to the other subgroups (one way ANOVA, F = 3.57, p = 0.032) CONCLUSIONS : even though further controlled studies are needed to clarify the relationship between age at onset and outcome in BD, the present follow-up study suggests clinical peculiarities and different patterns of response to mood stabilizers across distinct subgroups of patients with BD and different ages at onset

Activations in gray and white matter are modulated by uni-manual responses during within and inter-hemispheric transfer: effects of response hand and right-handedness

Because the visual cortices are contra-laterally organized, inter-hemispheric transfer tasks have been used to behaviorally probe how information briefly presented to one hemisphere of the visual cortex is integrated with responses resulting from the ipsi- or contra-lateral motor cortex. By forcing rapid information exchange across diverse regions, these tasks robustly activate not only gray matter regions, but also white matter tracts. It is likely that the response hand itself (dominant or non-dominant) modulates gray and white matter activations during within and inter-hemispheric transfer. Yet the role of uni-manual responses and/or right hand dominance in modulating brain activations during such basic tasks is unclear. Here we investigated how uni-manual responses with either hand modulated activations during a basic visuo-motor task (the established Poffenberger paradigm) alternating between inter- and within-hemispheric transfer conditions. In a large sample of strongly right-handed adults (n = 49), we used a factorial combination of transfer condition [Inter vs. Within] and response hand [Dominant(Right) vs. Non-Dominant (Left)] to discover fMRI-based activations in gray matter, and in narrowly defined white matter tracts. These tracts were identified using a priori probabilistic white matter atlases. Uni-manual responses with the right hand strongly modulated activations in gray matter, and notably in white matter. Furthermore, when responding with the left hand, activations during inter-hemispheric transfer were strongly predicted by the degree of right-hand dominance, with increased right-handedness predicting decreased fMRI activation. Finally, increasing age within the middle-aged sample was associated with a decrease in activations. These results provide novel evidence of complex relationships between uni-manual responses in right-handed subjects, and activations during within- and inter-hemispheric transfer suggest that the organization of the motor system exerts sophisticated functional effects. Moreover, our evidence of activation in white matter tracts is consistent with prior studies, confirming fMRI-detectable white matter activations which are systematically modulated by experimental condition

Longitudinal investigation of the parietal lobe anatomy in bipolar disorder and its association with general functioning

The parietal lobe (PL) supports cognitive domains, including attention and memory, which are impaired in bipolar disorder (BD). Although cross-sectional voxel-based morphometry studies found reduced PL grey matter (GM) in BD, none has longitudinally focused on PL anatomy in BD, relating it to patients? functioning. Thirty-eight right-handed BD patients and 42 matched healthy subjects (HS) underwent a Magnetic Resonance Imaging (MRI) scan at baseline. Seventeen BD patients and 16 matched HS underwent a follow-up MRI. PL white matter (WM) and GM volumes were measured. The trajectory of parietal volumes over time and the possible relation with the global functioning were investigated in both BD patients and HS. At baseline, BD patients showed significant reduced PL WM and GM and different WM laterality compared with HS. Furthermore, smaller PL WM volumes predicted lower global functioning in BD, but not in HS. At follow-up, although BD patients reported reduced PL WM compared with HS, no different pattern of volume changes over time was detected between groups. This study suggests the involvement of the PL in the pathophysiology of BD. In particular, PL WM reductions seem to predict an impairment in general functioning in BD and might represent a marker of functional outcome

Validity and reliability of the Structured Clinical Interview for the Trauma and Loss Spectrum (SCI-TALS)

Background. DSM-IV identifies three stress response disorders (acute stress Disorder (ASD), post-traumatic stress Disorder (PTSD) and adjustment disorders (AD)) that derive from specific life events. An additional condition of complicated grief (CG), well described in the literature, is triggered by bereavement. This paper reports on the reliability and validity of the Structured Clinical Interview for Trauma and Loss Spectrum (SCI-TALS) developed to assess the spectrum of stress response. The instrument is based on a spectrum model that emphasizes soft signs, low-grade symptoms, subthreshold syndromes, as well as temperamental and personality traits comprising clinical and subsyndromal manifestations. Methods. Study participants, enrolled at 6 Italian Departments of Psychiatry located at six sites, included consecutive patients with PTSD, 44 with CG and a comparative group of 48 unselected controls. Results. We showed good reliability and validity of the SCI-TALS. Domain scores were significantly higher in participants with PTSD or CG compared to controls. There were high correlations between specific SCI-TALS domains and corresponding scores on established measures of similar constructs. Participants endorsing grief and loss events reported similar scores on all instruments, except those with CG who scored significantly higher on the domain of grief reactions. Conclusion. These findings provide strong support for the internal consistency, the discriminant validity and the reliability of the SCI-TALS. These results also support the existence of a specific grief-related condition and the proposal that different forms of stress response have similar manifestations