Functional Impairment and Cognition in Bipolar Disorder

Bipolar disorder is a common, chronic and severe mental disorder, affecting approximately 2% of the adult population. Bipolar disorder causes substantial psychosocial morbidity that frequently affects the patient's marriage, children, occupation, and other aspects of the patient's life. Few studies have examined the functional impairment in patients with affective illness. Earlier outcome studies of mania reported favorable long-term outcomes. However, modern outcome studies have found that a majority of bipolar patients evidence high rates of functional impairment. These low reports of functional recovery rates are particularly surprising. The basis for such limited functional recovery is not entirely clear. Factors associated with functional dysfunction include presence of inter-episode symptoms, neuroleptic treatment, lower social economic class, and lower premorbid function. Cognitive dysfunction, a symptom domain of schizophrenia, has been identified as an important measure of outcome in the treatment of schizophrenia. Recently, there has been some suggestion that there may be impaired neuropsychological performance in euthymic patients with recurring mood disorders. Whether impaired neuropsychological performance in associated with the functional impairment in bipolar patients who have achieved syndromal recovery is an intriguing question. The literature on functional impairment and cognition in bipolar disorder is reviewed.     

Functional Impairment in Patients with Panic Disorder

Objective Anxiety and depression and sociodemographic factors such as age, gender, education level, income, and marital status among people with panic disorder (PD) are associated with functional impairment in the areas of work, social, and family. Although both PD-specific scales such as the Panic Disorder Severity Scale (PDSS) and Anxiety Sensitivity Inventory-Revised (ASI-R) and early trauma have been investigated, their relationship with functional impairment in PD patients has not been clarified. Methods This study included 267 PD patients. The PDSS, Beck Depression Inventory (BDI), ASI-R, and Early Trauma Inventory were used. Pearson’s correlation and multiple linear regression analyses were performed. The Sheehan Disability Scale (SDS) was administered to assess the functional impairment level in PD patients. Results Our findings showed that high levels of PDSS, BDI, and ASI-R were significantly correlated with the functional impairment among PD patients. Multiple regression analyses showed that PDSS, BDI, and ASI-R can predict the functional impairment levels, and PDSS and ASI-R were significantly associated with lost and underproductive days in PD patients. Conclusion Panic-specific symptoms, depression, and AS are associated with functional impairment level in PD patients. Elevated symptom severity can play a role by affecting productivity and daily responsibilities in PD patients.     

Functional Impairment,Stress, and Psychosocial Intervention in Bipolar Disorder

The longitudinal course of bipolar disorder (BD) is highly impairing. This article reviews recent research on functional impairment in the course of BD, the roles of social and intrafamilial stress in relapse and recovery, and the role of adjunctive psychosocial interventions in reducing risk and enhancing functioning. Comparative findings in adult and childhood BD are highlighted. Life events and family-expressed emotion have emerged as significant predictors of the course of BD. Studies of social information processing suggest that impairments in the recognition of facial emotions may characterize both adult- and early-onset bipolar patients. Newly developed psychosocial interventions, particularly those that focus on family and social relationships, are associated with more rapid recovery from episodes and better psychosocial functioning. Family-based psychoeducational approaches are promising as early interventions for children with BD or children at risk of developing the disorder. For adults, interpersonal therapy, mindfulness-based strategies, and cognitive remediation may offer promise in enhancing functioning.     

Resting-State fMRI Connectivity Impairment in Schizophrenia and Bipolar Disorder

Background: Schizophrenia and bipolar disorder share aspects of phenomenology and neurobiology and thus may represent a continuum of disease. Few studies have compared connectivity across the brain in these disorders or investigated their functional correlates. Methods: We used resting-state functional magnetic resonance imaging to evaluate global and regional connectivity in 32 healthy controls, 19 patients with bipolar disorder, and 18 schizophrenia patients. Patients also received comprehensive neuropsychological and clinical assessments. We computed correlation matrices among 266 regions of interest within the brain, with the primary dependent measure being overall global connectivity strength of each region with every other region. Results: Patients with schizophrenia had significantly lower global connectivity compared with healthy controls, whereas patients with bipolar disorder had global connectivity intermediate to and significantly different from those of patients with schizophrenia and healthy controls. Post hoc analyses revealed that compared with healthy controls, both patient groups had significantly lower connectivity in the paracingulate gyrus and right thalamus. Patients with schizophrenia also had significantly lower connectivity in the temporal occipital fusiform cortex, left caudate nucleus, and left thalamus compared with healthy controls. There were no significant differences among the patient groups in any of these regions. Lower global connectivity among all patients was associated with worse neuropsychological and clinical functioning, but these effects were not specific to any patient group. Conclusions: These findings are consistent with the hypothesis that schizophrenia and bipolar disorder may represent a continuum of global disconnectivity in the brain but that regional functional specificity may not be evident.Key words: resting-state fMRI, schizophrenia, bipolar disorder, connectivity     

Increased Suicidal Ideation in Patients with Co-Occurring Bipolar Disorder and Post-Traumatic Stress Disorder

Suicide risk increases for those with Bipolar Disorder or PTSD, however little research has focused on risk for co-occurring Bipolar Disorder and PTSD. The aim of this article was to evaluate increased suicide risk in co-occurring disorders, and differences in suicide risk for patients with Bipolar I versus Bipolar II. This study evaluated suicide risk in patients with co-occurring PTSD and Bipolar Disorder (n = 3,158), using the MADRS and Suicide Questionnaire. Those with history of PTSD had significantly higher suicidal ideation than those without (U = 1063375.00, p < .0001). Those with Bipolar I had higher risk than those with Bipolar II. Patients with Bipolar I and PTSD were at higher risk for suicidal ideation, implying the importance of diagnosis and risk assessment.     

Increased BDNF Levels in Long-term Bipolar Disorder Patients

IntroductionBipolar disorder (BD) is a prevalent, chronic and progressive illness. There is a growing body of evidence indicating that brain-derived neurotrophic factor (BDNF) plays an important role in the pathophysiology of BD.ObjectiveThe aim of this study was to evaluate BDNF plasma levels in BD patients with long term illness in comparison with controls.Methods87 BD type I patients and 58 controls matched by age, gender and education level were enrolled in this study. All subjects were assessed by the Mini-International Neuropsychiatric Interview and the patients by the Young Mania Rating Scale and the Hamilton Depression Rating Scale. The plasma levels of BDNF were measured by ELISA.ResultsOn average, patients had suffered from BD for 23.4 years. In comparison with controls, BD patients with mania presented a 1.90-fold increase in BDNF plasma levels (p = .001), while BD patients in remission presented a 1.64-fold increase in BDNF plasma levels (p = .03). BDNF plasma levels were not influenced by age, length of illness or current medications.ConclusionsThe present study suggests that long-term BD patients exhibit increased circulating levels of BDNF.     

Aberrant Resting-State Functional Connectivity in the Default Mode Network in Pediatric Bipolar Disorder Patients with and without Psychotic Symptoms

Mood disorders/psychosis have been associated with dysfunctions in the default mode network(DMN).However,the relative contributions of DMN regions to state and trait disturbances in pediatric bipolar disorder(PBD)remain unclear.The aim of this study was to investigate the possible mechanisms of PBD through brain imaging and explore the influence of psychotic symptoms on functional alterations in PBD patients.Twenty-nine psychotic and 26 non-psychotic PBD patients,as well as 19 age-and sex-matched healthy controls underwent a restingstate functional MRI scan and the data were analyzed by independent component analysis.The DMN component from the fMRI data was extracted for each participant.Spearman's rank correlation analysis was performed between aberrant connectivity and clinical measurements.The results demonstrated that psychotic PBD was characterized by aberrant DMN connectivity in the anterior cingulate cortex/medial prefrontal cortex,bilateral caudate nucleus,bilateral angular gyri,and left middle temporal gyrus,while non-psychotic PBD was not,suggesting further impairment with the development of psychosis.In summary,we demonstrated unique impairment in DMN functional connectivity in the psychotic PBD group.These specific neuroanatomical abnormalities may shed light on the underlying pathophysiology and presentation of PBD.     

血管性认知障碍患者的睡眠紊乱与非药物治疗

血管性认知障碍患者往往伴有睡眠障碍,睡眠的紊乱进一步降低了患者的生活质量,增加了其脑血管事件的风险,也加重了照料者的负担。有效治疗患者的睡眠障碍不仅可以改善其生活质量,对患者的认知及功能康复也有积极影响。本文对血管性认知障碍患者常见的睡眠紊乱进行综述,着重阐述了睡眠障碍非药物治疗方面的研究成果,并对这些治疗方法未来的研究方向以及在血管性认知障碍患者中的应用前景进行了探讨。     

Bipolar Disorder

Manic–depressive (bipolar) disorder is a severe, relapsing mental illness that shares characterstics both with major depressive disorder and with serious mental illnesses such as schizophrenia. Like schizophrenia, it is a chronic disorder, and is treated primarily in the specialty mental health sector. Rates of appropriate treatment are low. Functional outcome is compromised for the majority of individuals who have this disorder. Societal costs are exceeded only by those for schizophrenia. Existing cost calculations likely underestimate societal costs because of underestimating functional impact and neglecting to account for the substantial proportion of individuals who are institutionalized outside of the health care system (e.g., in prison). Little is known as yet regarding manic–depressive disorder in historically underserved groups and in vulnerable groups such as the elderly. There are major lacunae with regard to this disorder in the grant portfolios of all federal agencies mandated to address the needs of Americans with serious mental illnesses. The authors in the context of the Wider NIMH Affective Disorders Workgroup propose several specific recommendations to address the needs of this costly and underresearched disorder.     

Differentiating Patterns of Amygdala-Frontal Functional Connectivity in Schizophrenia and Bipolar Disorder

Background:

Insight into the neural mechanisms underlying the shared and disparate features of schizophrenia (SZ) and bipolar disorder (BD) is limited. The amygdala and prefrontal cortex (PFC) appear to have crucial roles in SZ and BD, yet abnormalities appear to manifest differently in the 2 disorders.

Methods:

Eighteen participants with SZ, 18 participants with BD, and 18 healthy controls (HC) underwent resting-state functional magnetic resonance imaging. Resting-state functional connectivity (rsFC) between the PFC and the amygdala divided into 3 subregions (the laterobasal, centromedial, and superficial amygdala) was examined using probabilistic anatomic maps. For each participant, rsFC maps of the 3 amygdala subregions were computed and compared across the 3 groups.

Results:

Compared with the HC group, we found significant differences in rsFC between the amygdala and PFC in the SZ and BD groups. In direct comparison between the SZ and BD groups, distinct patterns of rsFC between the amygdala and PFC were observed, particularly in the superficial amygdala. RsFC between the amygdala and the dorsal lateral PFC was significantly decreased in the SZ group, whereas rsFC between the amygdyala and the ventral PFC was significantly decreased in the BD group.

Conclusions:

These results strongly suggest dorsal vs ventral PFC differentiation in amygdala-PFC neural system abnormalities between SZ and BD. These regional differences in SZ and BD may give rise to the differences in clinical characteristics observed in SZ and BD, and may implicate potential avenues for differentiating the 2 disorders during early stages of illness.Key words: schizophrenia, bipolar disorder, resting state, functional connectivity, amygdala, prefrontal cortexSchizophrenia (SZ) and bipolar disorder (BD) have long been viewed as separate neuropsychiatric disorders; however, the distinctiveness of these 2 disorders from each other has also long been questioned. SZ and BD have shared symptomatology, and neurocognitive deficits persist in affected individuals in both disorders.¹ Additionally, SZ and BD share similar susceptibility genes² and frequently co-occur within families.³ While the debate regarding the distinctions between SZ and BD continues, understanding of the neural basis for the shared and disparate features of the 2 disorders remains limited. Recently, convergent evidence suggests disruptions within the frontotemporal neural systems that subserve emotional and cognitive processing in both SZ and BD, including abnormalities in 2 regions with critical roles in this system, the amygdala and prefrontal cortex (PFC).^4,5While it appears that the amygdala and PFC are shared regions for abnormalities in SZ and BD, the manifestation of abnormalities within these regions may differ between the 2 disorders. Postmortem histological studies provide preliminary evidence of reduced amygdala volumes and alterations in gene expression in the amygdala in SZ.^6,7 Reduced amygdala volumes in SZ have been confirmed by several magnetic resonance image (MRI) studies and recent meta-analysis studies.^8,9 Postmortem histological studies have also demonstrated abnormalities in the amygdala in BD. These studies have shown decreased glial density and neuron somal size in the amygdala in BD.^7,10 However, while decreased amygdala volume is one of the most consistent neuroimaging findings in pediatric BD,¹¹ findings of abnormalities in amygdala volume in adult BD, although frequently reported, are inconsistent.¹²With respect to the PFC, previous studies have found differences in frontal activation between SZ and BD using task-related functional MRI.^13,14 Moreover, other studies have found decreased activation in the dorsal PFC in SZ,^15,16 whereas studies using similar methods have found altered activation in the ventral PFC (VPFC) in BD.^17,18 In this article, the dorsal PFC is defined as including the dorsal lateral PFC (DLPFC) and dorsal anterior cingulate cortex (ACC), and the VPFC is defined as including the orbitofrontal cortex (OFC), the inferior and rostral frontal cortices, ventral and rostral components of the ACC. These contrasting PFC described above are of considerable interest as the dorsal PFC has been associated with working memory impairment, a core cognitive process abnormality in SZ.¹⁹ Whereas the VPFC has been associated with hedonic processes²⁰ linked to the core psychopathology of BD.The regional differences between SZ and BD observed in the PFC (dorsal vs ventral) suggest that differences between the 2 disorders may also exist in the connectivity between the PFC and regions such as the amygdala. The amygdala has multiple reciprocal channels of communication with the dorsal PFC through the hippocampus,²¹ and it is highly interconnected with the VPFC.²² The cingulum and uncinate fasciculus provide substantial connections between the amygdala and the dorsal and ventral PFC.^23–25 Additionally, the amygdala is a complex structure comprised of multiple nuclei with varied function and roles. Differences in human resting-state FC (rsFC) patterns of the laterobasal (LB), centromedial (CM), and superficial (SF) amygdala have been previously reported in a recent resting-state fMRI study in healthy control (HC) individuals.²⁶ Moreover, the SF amygdala has been particularly implicated in emotional processing, for which differences between SZ and BD have been demonstrated.^27,28In recent years, rsFC has been successfully applied for mapping complex neural circuits. Coherent spontaneous blood oxygen level-dependent (BOLD) activity during rest among specific subsets of brain regions is thought to reflect the natural organization of brain networks and may have significant implications regarding the pathophysiology of psychiatric disorders. We are not aware of any studies directly comparing SZ and BD with regards to rsFC between the amygdala and PFC.In this study, we utilized a region-of-interest (ROI)–based approach to examine rsFC in individuals with SZ and BD, and HC participants. We selected the amygdala as the ROI and focused on its rsFC with the PFC. Given the differences in function and rsFC within the amygdala, we examined the amygdala as 3 subregions, the LB, CM, and SF amygdala, to explore rsFC differences between these subregions and the PFC in the 3 groups (SZ, BC, and HC). Subdivision of the amygdala in this study was based on known differences in functional roles and connections with other brain regions and a recently developed stereotaxic, cytoarchitectonic maps.²⁹ We hypothesized that both the SZ and BD groups would show altered rsFC between the amygdala and PFC when compared with the HC group; furthermore, we hypothesized that, in direct comparison between the SZ and BD groups, altered rsFC between the amygdala and dorsal PFC would be more prominent in SZ, whereas it would be more prominent with the VPFC in BD.