Psychosocial and neurocognitive profiles in depressed patients with major depressive disorder and bipolar disorder

Previous studies have revealed psychosocial and cognitive impairments in patients during depression. The primary aim of this study was to investigate whether patients with major depression (MDD) and bipolar disorder (BD) differ in psychosocial and neurocognitive profiles. A second aim was to examine whether cognitive impairments are homogeneous among depressed patients. Patients with MDD (n = 16) and BD (n = 14) were enrolled during a major depressive episode. About half of them had comorbidities, including personality, substance use, and anxiety disorders. Information was collected about symptomatology and psychosocial functioning, whereas an exhaustive neuropsychological battery was administered to assess cognition. During a depressive episode, MDD and BD patients had global psychosocial dysfunction, characterized by occupational and relational impairments. A cognitive slowing was also observed, as well as deficits related to alertness, spontaneous flexibility, sustained and divided attention. Moreover, severity of depression and cognitive functions were significantly associated with psychosocial functioning. In the case of severe mood disorders, psychosocial and neurocognitive functioning seem similar among MDD and BD patients during a depressive episode. In addition to an altered daily functioning, the neurocognitive profile was heterogeneous with regard to the nature and extent of cognitive deficits. Executive functions, as well as verbal learning and memory, were preserved better than attentional processes.     

Patterns of memory impairment in bipolar disorder and unipolar major depression

Unipolar and bipolar depression are known to exert detrimental effects on learning and memory processes. However, few comparisons have been undertaken between bipolar and unipolar patients with comparable illness histories, and predictors of impairment are not well understood. Adult outpatients with unipolar major depressive illness (UP, n = 30) and bipolar disorder (BP, n = 30), group-matched for illness duration and severity of depressive symptomatology (16% clinically remitted, 42% partially remitted, 42% depressed), and 30 demographically matched controls completed measures of general cognitive functioning and declarative memory. Despite comparable general intellectual abilities, BP and UP patients exhibited significant memory deficits relative to healthy controls. A similar deficit profile was observed in both patient groups, involving poorer verbal recall and recognition. Impairments were not secondary to strategic processing deficits or rapid forgetting. Although depression severity was not associated with neurocognitive performance, number of hospitalizations and family history of mood disorder significantly affected memory function in BP, but not UP, patients. Results suggest qualitatively similar patterns of memory impairment in BP and UP patients, consistent with a primary encoding deficit. These impairments do not appear to be secondary to clinical state, but rather suggest a similar underlying pathophysiology involving medial temporal dysfunction.     

Intensive psychosocial intervention enhances functioning in patients with bipolar depression: results from a 9-month randomized controlled trial

OBJECTIVE: Psychosocial interventions are effective adjuncts to pharmacotherapy in delaying recurrences of bipolar disorder; however, to date their effects on life functioning have been given little attention. In a randomized trial, the authors examined the impact of intensive psychosocial treatment plus pharmacotherapy on the functional outcomes of patients with bipolar disorder over the 9 months following a depressive episode. METHOD: Participants were 152 depressed outpatients with bipolar I or bipolar II disorder in the multisite Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study. All patients received pharmacotherapy. Eighty-four patients were randomly assigned to intensive psychosocial intervention (30 sessions over 9 months of interpersonal and social rhythm therapy, cognitive behavior therapy [CBT], or family-focused therapy), and 68 patients were randomly assigned to collaborative care (a 3-session psychoeducational treatment). Independent evaluators rated the four subscales of the Longitudinal Interval Follow-Up Evaluation-Range of Impaired Functioning Tool (LIFE-RIFT) (relationships, satisfaction with activities, work/role functioning, and recreational activities) through structured interviews given at baseline and every 3 months over a 9-month period. RESULTS: Patients in intensive psychotherapy had better total functioning, relationship functioning, and life satisfaction scores over 9 months than patients in collaborative care, even after pretreatment functioning and concurrent depression scores were covaried. No effects of psychosocial intervention were observed on work/role functioning or recreation scores during this 9-month period. CONCLUSIONS: Intensive psychosocial treatment enhances relationship functioning and life satisfaction among patients with bipolar disorder. Alternate interventions focused on the specific cognitive deficits of individuals with bipolar disorder may be necessary to enhance vocational functioning after a depressive episode.     

RESEARCH: Cognitive Rehabilitation for Bipolar Disorder: An Open Trial for Employed Patients with Residual Depressive Symptoms

Bipolar disorder is characterized by recurrent episodes of depression and/or mania along with interepisodic mood symptoms that interfere with psychosocial functioning. Despite periods of symptomatic recovery, individuals with bipolar disorder often continue to experience impairments in psychosocial functioning, particularly occupational functioning. Two determinants of psychosocial functioning of euthymic (neither fully depressed nor manic) individuals with bipolar disorder are residual depressive symptoms and cognitive impairment (i.e., difficulties with executive functioning, attention, and memory). The present study explored whether a new cognitive remediation (CR) treatment designed to treat residual depressive symptoms and, for the first time to the best of our knowledge, address cognitive impairment would be associated with improvement in psychosocial functioning in individuals with bipolar disorder. Following a neuropsychological and clinical assessment 18 individuals with DSM‐IV bipolar disorder were treated with 14 individual sessions of CR. Results indicated that at the end of treatment, as well as at the 3‐months follow‐up, patients showed lower residual depressive symptoms, and increased occupational, as well as overall psychosocial functioning. Pretreatment neuropsychological impairment predicted treatment response. Improvements in executive functioning were associated with improvements in occupational functioning. These findings suggest that treating residual depressive symptoms and cognitive impairment may be an avenue to improving occupational and overall functioning in individuals with bipolar disorder.     

Serum brain-derived neurotrophic factor in bipolar and unipolar depression: A potential adjunctive tool for differential diagnosis

The differential diagnosis of Bipolar Disorder (BD) and Major Depressive Disorder (MDD) is a diagnostic challenge during depressive episodes. Noteworthy, the proper differentiation between BD depressive state and MDD has important treatment implications. BDNF levels may be valuable adjunctive tool for this differential diagnosis. Ten subjects with MDD, forty with BD type I and thirty healthy comparison subjects were recruited. All subjects had BDNF serum levels measured and, in patients, BDNF serum levels were assessed during acute depressive episode. Optimal sensitivity and specificity of serum BDNF for the differential diagnosis of unipolar and bipolar depression were determined by the receiver operating characteristic (ROC) curve analysis, using a nonparametric approach. Serum BDNF levels in depressive BD patients were lower compared to MDD patients and controls (0.15 ± 0.08, 0.35 ± 0.08, and 0.38 ± 0.12, respectively, p < 0.001). The area under the curve (AUC) of the ROC analysis in BD depression vs. MDD was 0.95 (ranged from 0.89 to 1.00). Overall, the AUC of the ROC analysis (BD depression vs. MDD and controls) was 0.94 (95% CI 0.89 to 0.99, p < 0.001). A proposed “best” cutoff of 0.26 resulted in 88% sensitivity and 90% specificity. Serum BDNF levels appear as a promising tool to discriminate bipolar from unipolar depression. Our results suggest the role of BDNF as an adjunctive tool to promote prompt and accurate diagnosis of BD. However, further investigation and replication of these results are warranted.     

Neurocognitive functioning in patients recently diagnosed with bipolar disorder

Hellvin T, Sundet K, Simonsen C, Aminoff SR, Lagerberg TV, Andreassen OA, Melle I. Neurocognitive functioning in patients recently diagnosed with bipolar disorder. Bipolar Disord 2012: 14: 227–238. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objectives: Cognitive dysfunction in bipolar disorder (BD) is well established in the literature; however, there are few studies of neurocognition in patients early in the course of the illness. In this study we compare neurocognitive function in a cohort of first‐contact mania patients with a healthy control group matched for age, gender, and education. Methods: Patients with a first manic episode (FM) (n = 34) or previous untreated manic episodes (PM) (n = 21) were neuropsychologically tested following their first treated manic episode. A total of 110 matched healthy control comparison subjects were also tested. The following cognitive domains were evaluated: verbal and visual learning and memory, attention, processing speed, executive functioning, and IQ. Results were corrected for speed of processing differences and were compared with previously reported results for multiple‐episode BD patients. Results: BD patients early in their disease course showed impairments in psychomotor speed, attention, learning and memory, executive functioning, and IQ. When controlling for speed of processing, measures of visuoconstructive reasoning and motor dexterity remained statistically significant. Eighteen percent of FM and 16% of PM patients were found to have clinically significant neurocognitive impairment. No significant relationship between clinical symptoms and neurocognition was found. The first‐contact mania patients studied were found to have smaller neurocognitive deficits compared to multiple‐episode patients in previous studies. Conclusions: Neurocognitive dysfunction is present in early BD and is clinically significant for a proportion of patients. Our findings also suggest that neurocognitive dysfunction may increase with illness progression.     

Distinct profiles of neurocognitive function in unmedicated unipolar depression and bipolar II depression.

BACKGROUND: Studies have demonstrated neuropsychological deficits across a variety of cognitive domains in depression. Few studies have directly compared depressed subjects with major depressive disorder (MDD) and bipolar disorder (BD), and many are confounded by medication status across subjects. In this study, we compared the performance of unmedicated currently depressed MDD and BD groups on a battery of neuropsychological tests that included measures of risk taking and reflection impulsivity. METHODS: Twenty-two MDD, seventeen BDII, and 25 healthy control subjects (HC), matched for age and IQ, were assessed on a battery of neuropsychological tests. RESULTS: The depressed groups showed comparable ratings of depression severity and age of illness onset. The MDD group was impaired on tests of spatial working memory and attentional shifting, sampled less information on a test of reflection impulsivity, and was oversensitive to loss trials on a decision-making test. The BDII subjects were generally intact and did not differ significantly from control subjects on any test. CONCLUSIONS: These data indicate differing profiles of cognitive impairment in unmedicated depressed MDD versus BDII subjects. Moderately depressed BDII subjects displayed relatively intact cognitive function, whereas MDD subjects demonstrated a broader range of executive impairments. These cognitive deficits in depression were not attributable to current medication status.     

Impaired verbal memory in young adults with unipolar and bipolar depression

Aim: Early stages of severe mood disorders may be accompanied by neurocognitive changes. Specifically, deficits in verbal memory have been linked to depression in young people. This study examined whether young adults with unipolar compared with bipolar depression showed similar neurocognitive deficits. Methods: A total of 57 young adults (16–32 years) were assessed in this study. Twenty with unipolar and 20 with bipolar depression, all currently depressed, were compared with 17 healthy controls. Neuropsychological assessment included psychomotor speed, attention for routine mental operations, attentional switching, executive control and verbal learning and memory. Results: Both unipolar and bipolar subjects showed significant impairments in verbal memory and attentional switching compared with controls. Both mood disorder groups showed no impairments in psychomotor speed, attention for routine mental operations and executive control. Effects size calculations show that the unipolar and bipolar groups do not differ from each other across a range of neurocognitive measures. Conclusion: Neurocognitive deficits in young adults with current depressive syndromes appear to differ from those typically seen in older patients. In early adulthood, both unipolar and bipolar depression may be distinguished by poor verbal memory, despite intact speed of processing, attention and executive functions. This study suggests that there is utility in neuropsychological testing for young adults in the early stages of severe mood disorders. In order to prevent neurobiological changes inherent to the disease, pharmacological and non-pharmacological interventions that target verbal memory deficits may be optimally delivered early in the disease course.     

Neurocognitive performance in children and adolescents with bipolar disorder: a review

A number of studies have reported the evidence of cognitive deficits in adult bipolar patients. Recently, there has been a shift in research on neurocognitive performance in bipolar disorder (BD) towards examining younger age groups. A review of the literature on neurocognitive impairments in BD in childhood and adolescence was conducted. We searched systematically for studies in samples of age groups younger than 18 years of age in average that included either a healthy control group or normative data for the cognitive tests used. Twenty-one original articles were found and reviewed. Children and adolescents with BD show deficits in a variety of cognitive areas. The most consistent results were found for impairments in verbal memory. A majority of studies also indicated impairments in working memory. Similar pattern of neurocognitive impairment was found in children and adolescents as compared to adults suffering from BD. The neurocognitive deficits need to be recognized and incorporated into individual treatment programs.     

Comparison of clinical characteristics of bipolar and depressive disorders in Korean clinical sample of youth: a retrospective chart review

The purpose of this study was to compare the clinical characteristics of bipolar disorder I, II (BD I and II) and not otherwise specified (BD NOS) to those of major depressive disorder (MDD) in a clinical sample of Korean children and adolescents. This study was a cross-sectional review of longitudinal observational data. Two psychiatrists retrospectively reviewed the medical records of 198 children and adolescents (age 6–18) that were diagnosed as having bipolar or depressive disorders from March 2010 to February 2012 at Department of Psychiatry of Asan Medical Center, Seoul, Korea. Every subject’s diagnoses were reviewed and confirmed. BD I, II and MDD were assessed according to the Diagnostic and Statistical Manual-IV criteria. BD NOS was defined based on the criteria for the Course and Outcome of Bipolar Youth study. Comparisons were made in demographic information, clinical characteristics, family history, and psychiatric comorbidities at baseline and during observation. Among 198 subjects, 20 (10.1 %) subjects were diagnosed as having BD I, 10 (5.1 %) as BD II, 25 (12.6 %) as BD NOS and 143 (73.7 %) as MDD. BD depression was associated with mood change while taking an antidepressant, familial bipolarity, aggressive behaviors, and atypical features. Comorbid obsessive–compulsive disorder tended to be higher in BD NOS than in MDD. Presence of psychosocial stressors was more common in MDD than in BD depression. In children and adolescents, bipolar depression is distinct from unipolar depression in family history, comorbidity, and clinical characteristics.     

Psychosocial disability during the long-term course of unipolar major depressive disorder

BACKGROUND: The goal of this study was to investigate psychosocial disability in relation to depressive symptom severity during the long-term course of unipolar major depressive disorder (MDD). METHODS: Monthly ratings of impairment in major life functions and social relationships were obtained during an average of 10 years' systematic follow-up of 371 patients with unipolar MDD in the National Institute of Mental Health Collaborative Depression Study. Random regression models were used to examine variations in psychosocial functioning associated with 3 levels of depressive symptom severity and the asymptomatic status. RESULTS: A progressive gradient of psychosocial impairment was associated with a parallel gradient in the level of depressive symptom severity, which ranges from asymptomatic to subthreshold depressive symptoms to symptoms at the minor depression/dysthymia level to symptoms at the MDD level. Significant increases in disability occurred with each stepwise increment in depressive symptom severity. CONCLUSIONS: During the long-term course, disability is pervasive and chronic but disappears when patients become asymptomatic. Depressive symptoms at levels of subthreshold depressive symptoms, minor depression/ dysthymia, and MDD represent a continuum of depressive symptom severity in unipolar MDD, each level of which is associated with a significant stepwise increment in psychosocial disability.     

Neuropsychologic impairments in bipolar and unipolar mood disorders on the CANTAB neurocognitive battery.

BACKGROUND: Cognitive deficits associated with mood disorders, especially bipolar disorder, have been the focus of limited systematic investigation. METHODS: We tested 35 bipolar (21 in depressed state and 14 in mixed or manic state) and 58 nonbipolar depressed consecutively admitted young adult inpatients and 51 matched healthy individuals on the Cambridge Neuropsychological Test Automated Battery, a computerized neurocognitive battery. RESULTS: The mixed/manic bipolar patients demonstrated robust deficits in episodic and working memory, spatial attention, and problem solving. In contrast, depressed bipolar and nonbipolar patients demonstrated impairments only in episodic memory. CONCLUSIONS: Neuropsychologic findings with the Cambridge Neuropsychological Test Automated Battery indicate widely distributed deficits in cognitive domains subserved by temporal, parietal, and frontostriatal systems in bipolar patients during mixed/manic states of illness. Significant deficits in bipolar and nonbipolar depressed patients were restricted to episodic memory, suggesting a more selective dysfunction in mesial temporal lobe function during episodes of depression. These findings highlight the different cognitive profiles of mania and depression, demonstrate similar patterns of neuropsychologic deficits in bipolar and nonbipolar depression, and point to a need for further research investigating the characteristics, causes, course, and treatment of severe cognitive deficits associated with mixed/manic phases of bipolar disorder.     

Pharmacological approaches in bipolar disorders and the impact on cognition: a critical overview

Dias VV, Balanzá‐Martinez V, Soeiro‐de‐Souza MG, Moreno RA, Figueira ML, Machado‐Vieira R, Vieta E. Pharmacological approaches in bipolar disorders and the impact on cognition: a critical overview. Objective: Historically, pharmacological treatments for bipolar disorders (BD) have been associated with neurocognitive side‐effects. We reviewed studies which assessed the impact of several psychopharmacological drugs on the neurocognitive function of BD patients. Method: The PubMed database was searched for studies published between January 1980 and February 2011, using the following terms: bipolar, bipolar disorder, mania, manic episode, or bipolar depression, cross‐referenced with cognitive, neurocognitive, or neuropsychological, cross‐referenced with treatment. Results: Despite methodological flaws in the older studies and insufficient research concerning the newer agents, some consistent findings emerged from the review; lithium appears to have definite, yet subtle, negative effects on psychomotor speed and verbal memory. Among the newer anticonvulsants, lamotrigine appears to have a better cognitive profile than carbamazepine, valproate, topiramate, and zonisamide. More long‐term studies are needed to better understand the impact of atypical antipsychotics on BD patients’ neurocognitive functioning, both in monotherapy and in association with other drugs. Other agents, like antidepressants and cognitive enhancers, have not been adequately studied in BD so far. Conclusion: Pharmacotherapies for BD should be chosen to minimize neurocognitive side‐effects, which may already be compromised by the disease process itself. Neurocognitive evaluation should be considered in BD patients to better evaluate treatment impact on neurocognition. A comprehensive neuropsychological evaluation also addressing potential variables and key aspects such as more severe cognitive deficits, comorbidities, differential diagnosis, and evaluation of multiple cognitive domains in longitudinal follow‐up studies are warranted.     

Neurocognitive profiles in bipolar I and bipolar II disorder: differences in pattern and magnitude of dysfunction

Objectives:  Studies on neurocognitive functioning in bipolar disorder, reporting deficits in memory, attention, and executive functioning, have primarily focused on bipolar I disorder. The aim of this study was to examine whether patients with bipolar I and bipolar II disorder have different neurocognitive profiles.
Methods:  Forty-two patients with bipolar I disorder, 31 patients with bipolar II and 124 healthy controls, from a large ongoing study on psychotic disorders, were included. Neurocognitive function was measured with a comprehensive neuropsychological test battery.
Results:  The bipolar I group performed significantly poorer than the healthy control group and the bipolar II group on all measures of memory. Compared with the control group, the bipolar I group also had significantly reduced performance on most measures of attention and executive functioning, while the bipolar II group only had a significantly reduced performance on a subset of these measures. On average, 24% of the bipolar I group had clinically significant cognitive impairment (≤1.5 SD below the control group mean) across measures, compared with 13% of the bipolar II group.
Conclusions:  Patients with bipolar I and bipolar II disorder in this study have different neurocognitive profiles. Bipolar I patients have more widespread cognitive dysfunction both in pattern and magnitude, and a higher proportion has clinically significant cognitive impairments compared with patients with bipolar II. This may suggest neurobiological differences between the two bipolar subgroups.     

Neurocognitive impairment and psychosocial functioning in bipolar II disorder

Solé B, Bonnin CM, Torrent C, Balanzá‐Martínez V, Tabarés‐Seisdedos R, Popovic D, Martínez‐Arán A, Vieta E. Neurocognitive impairment and psychosocial functioning in bipolar II disorder. Objective: There is a growing body of evidence on neurocognitive impairment in euthymic bipolar patients, but this issue has been studied mostly in bipolar I disorder, data on bipolar II (BD‐II) are scant and discrepant. The two aims of this study were to ascertain whether strictly defined euthymic BD‐II patients would present neurocognitive disturbances and to evaluate their impact on functional outcome. Method: Forty‐three BD‐II patients and 42 demographically and educationally matched healthy subjects were assessed with a comprehensive neuropsychological test battery and with the Social and Occupational Functioning Assessment Scale (SOFAS). The euthymia criteria were reduced (Hamilton Rating Scale for Depression score ≤6 and a Young Mania Rating Scale score ≤6) to minimize the influence of subdepressive symptomatology on cognition and functioning. Results: BD‐II patients showed a significantly lower performance on several measures of attention, learning and verbal memory, and executive function compared with healthy controls. The presence of subthreshold depressive symptomatology and one measure related to executive function (Trail Making Test, part B) was the variables that best predicted psychosocial functioning measured with the SOFAS. Conclusion: This report provides further evidence that euthymic BD‐II patients present cognitive impairment which may impact psychosocial functioning.     

Differences in Axis I and II comorbidity between bipolar I and II disorders and major depressive disorder

OBJECTIVE: To obtain a comprehensive view of differences in current comorbidity between bipolar I and II disorders (BD) and (unipolar) major depressive disorder (MDD), and Axis I and II comorbidity in BD in secondary-care psychiatric settings. METHOD: The psychiatric comorbidity of 90 bipolar I and 101 bipolar II patients from the Jorvi Bipolar Study and 269 MDD patients from the Vantaa Depression Study were compared. We used DSM-IV criteria assessed by semistructured interviews. Patients were inpatients and outpatients from secondary-care psychiatric units. Comparable information was collected on clinical history, index episode, symptom status, and patient characteristics. RESULTS: Bipolar disorder and MDD differed in prevalences of current comorbid disorders, MDD patients having significantly more Axis I comorbidity (69.1% vs. 57.1%), specifically anxiety disorders (56.5% vs. 44.5%) and cluster A (19.0% vs. 9.9%) and C (31.6% vs. 23.0%) personality disorders. In contrast, BD had more single cluster B personality disorders (30.9% vs. 24.6%). Bipolar I and bipolar II were similar in current overall comorbidity, but the prevalence of comorbidity was strongly associated with the current illness phase. CONCLUSIONS: Major depressive disorder and BD have somewhat different patterns in the prevalences of comorbid disorders at the time of an illness episode, with differences particularly in the prevalences of anxiety and personality disorders. Current illness phase explains differences in psychiatric comorbidity of BD patients better than type of disorder.     

Neuropsychological deficits and functional impairment in bipolar depression, hypomania and euthymia

OBJECTIVE: To examine whether patients with bipolar disorder (BD) have subtle neuropsychological deficits that manifest clinically as cognitive and functional compromise, and this study attempted to determine the pattern of such cognitive deficits and their functional impact across all three phases of BD. We hypothesised that euthymia does not equate with normal neuropsychological function and that each phase has a characteristic pattern of deficits, with disturbance in attention and memory being common across all phases of the illness: (i) bipolar depression - psychomotor slowing and impairment of memory; (ii) hypomania by frontal-executive deficits and (iii) euthymia - a mild disturbance of attention, memory and executive function. METHODS: Twenty-five patients with a diagnosis of bipolar I disorder underwent neuropsychological testing over a period of 30 months in the natural course of their illness while hypomanic and/or depressed and/or euthymic. The results from these assessments were compared with findings from neuropsychological tests conducted on 25 healthy controls matched for age, sex, education and handedness. RESULTS: Initial analyses revealed modest impairment in executive functioning, memory and attention in both hypomanic and depressed bipolar patients, with additional fine motor skills impairment in the latter. Memory deficits, also noted in euthymic patients, were non-significant after controlling for confounding variables, although bipolar depressed patients remained significantly impaired on tests of verbal recall. Bipolar depressed and hypomanic patients differed with respect to the nature of their memory impairment. Depressed patients were more impaired as compared with euthymic patients on tests of verbal recall and fine motor skills. Psychosocial functioning was impaired across all three patient groups, but only in depressed and hypomanic patients did this correlate significantly with neuropsychological performance. CONCLUSIONS: The mood-state-related cognitive deficits in both bipolar depression and hypomania compromise psychosocial function when patients are unwell. In euthymic patients, subtle impairments in attention and memory suggest that an absence of symptoms does not necessarily equate to 'recovery'. The possibility of persistent cognitive deficits in BD is an issue of profound clinical and research interest that warrants further investigation; however, future research needs to adopt more sophisticated neuropsychological probes that are able to better define state and trait deficits and determine their functional impact.     

Erythrocyte cation transport in endogenous depression: clinical and psychophysiological correlates

Clinical (psychometric), psychophysiological and biochemical (erythrocyte membrane transport) variables were studied in 44 patients with endogenous depression (unipolar/bipolar) during acute depressive episode and in remission. All parameters studied showed paralleled and unidirectional changes when depression was compared with remission period. During a depressive episode, unipolar patients had greater intensity of depression than bipolar patients. Ouabain-dependent sodium fluxes were significantly lower in female than in male patients during depression than in remission. In male bipolar patients, the indexes of active transport in erythrocytes showed significant correlations with clinical ratings and with results of psychophysiological tests. The results point to a possible relationship between various levels of physiological functioning in endogenous depression. This suggests a generalised "background" defect of energy-dependent membrane transport pertaining to both erythrocytes and nerve cells, which may be linked to disturbances of activational processes within the central nervous system.     

Neurocognitive functioning in bipolar disorder: What we know and what we don’t

Introduction: This narrative review of systematic reviews and meta-analyses aims at compiling available evidence in various aspects of neurocognitive functioning in Bipolar Disorder (BD).Methods: We conducted a MEDLINE literature search and identified 38 relevant systematic reviews and metaanalyses.Results: Current evidence suggests that BD is associated with cognitive impairment across multiple domains and during all clinical states. However, there is a considerable cognitive heterogeneity within BD, which cannot be explained by clinical subtypes, and the pattern of neurocognitive impairment in BD overlaps with other psychiatric conditions such as major depression and schizophrenia. Residual depressive symptoms, poor clinical course and higher number of manic episodes may negatively impact cognitive performance, which is a major predictor of general functioning in BD. Evidence from available prospective studies does not support the notion of progressive cognitive decline in BD while some evidence exists to suggest patients may show some improvements in cognitive functioning following the first manic episode. Furthermore, a subset of patients may show premorbid cognitive abnormalities that could signal an early neurodevelopmental aetiology. Preliminary findings from small studies identify potential pro-cognitive effects of Cognitive Remediation, erythropoietin, intranasal insulin, lurasidone, mifepristone, repetitive Transcranial Magnetic Stimulation and transcranial Direct Current Stimulation in BD.Discussion: Longitudinal studies in high-risk individuals can provide a better understanding of the development and progression of neurocognitive impairment in BD. Largescale randomised control trials are needed to compare the pro-cognitive efficacy of various pharmacological and non-pharmacological interventions in different cognitive subgroups of patients at different stages of BD.     

Mood symptoms, cognition, and everyday functioning: in major depression, bipolar disorder, and schizophrenia

People with depression, bipolar disorder, and schizophrenia manifest considerable cognitive deficits and impairments in everyday functional outcomes. The severity of current mood symptoms is associated with the severity of cognitive deficits in people with unipolar and bipolar disorder, but impairments are clearly still present in cases with minimal current mood symptoms. In people with schizophrenia, depression is less strongly associated with cognitive deficits on a cross-sectional basis, and some evidence suggests that depression and cognitive impairments are inversely related. Furthermore, in schizophrenia, mood symptoms seem to affect everyday functioning in a way that is unassociated with the severity of deficits in cognition and functional capacity. In contrast, in bipolar disorder, mood symptoms seem to affect real-world functioning through an adverse effect on the ability to perform critical functional skills. In both mood disorders and schizophrenia, depression appears to impact the motivation to perform potentially reinforcing acts, possibly through the induction of anhedonia. Clearly, depression has a major adverse impact on everyday functioning in all variants of severe mental illness, and improving its recognition (in the case of schizophrenia) and management has the potential to reduce the adverse impact of severe mental illness on everyday functioning. Reducing disability has the potential to have positive impacts in multiple objective and subjective aspects of functioning in severe mental illness.