Neuropsychological functions in patients with bipolar I and bipolar II disorder

Objectives:  The literature reports persistent cognitive impairments in patients with bipolar disorder even after prolonged remission. However, a majority of studies have focused only on bipolar I disorder (BP-I), primarily because bipolar II disorder (BP-II) is often underdiagnosed or misdiagnosed. More attention should be paid to the differences between BP-I and BP-II, especially the aspects of neuropsychological functioning. We examined the different neuropsychological functions in BP-I and BP-II patients and compared them with those of healthy controls.
Methods:  The study included 67 patients with interepisode bipolar disorder (BP-I: n = 30; BP-II: n = 37) and 22 healthy controls compared using a battery of neuropsychological tests that assessed memory, psychomotor speed, and certain aspects of frontal executive function.
Results:  The BP-I group performed poorly on verbal memory, psychomotor speed, and executive function compared to the BP-II and control groups. Both bipolar groups performed significantly less well than the control group on measures of working memory and psychomotor speed, while the BP-II group showed an intermediate level of performance in psychomotor speed compared to the BP-I and control groups. There was no difference between the groups on visual memory.
Conclusions:  BP-I was characterized by reduced performance in verbal memory, working memory, psychomotor speed, and executive function, while BP-II patients showed a reduction only in working memory and psychomotor speed. Cognitive impairment existed in both subtypes of bipolar disorder, and was greater in BP-I patients. Rehabilitation interventions should take into account potential cognitive differences between these bipolar subtypes.     

Phenomenology of children and adolescents with bipolar spectrum disorders

CONTEXT: Children and adolescents who present with manic symptoms frequently do not meet the full DSM-IV criteria for bipolar I disorder (BP-I). OBJECTIVE: To assess the clinical presentation and family history of children and adolescents with BP-I, bipolar II disorder (BP-II), and bipolar disorder not otherwise specified (BP-NOS). DESIGN: Subjects and their primary caretaker were assessed by semistructured interview, and family psychiatric history was obtained from interview of the primary caretaker. SETTING: Outpatient and inpatient units at 3 university centers. PARTICIPANTS: A total of 438 children and adolescents (mean +/- SD age, 12.7 +/- 3.2 years) with BP-I (n = 255), BP-II (n = 30), or BP-NOS (n = 153). MAIN OUTCOME MEASURES: Lifetime psychiatric history and family history of psychiatric disorders. RESULTS: Youth with BP-NOS were not diagnosed as having BP-I primarily because they did not meet the DSM-IV duration criteria for a manic or mixed episode. There were no significant differences among the BP-I and BP-NOS groups in age of onset, duration of illness, lifetime rates of comorbid diagnoses, suicidal ideation and major depression, family history, and the types of manic symptoms that were present during the most serious lifetime episode. Compared with youth with BP-NOS, subjects with BP-I had more severe manic symptoms, greater overall functional impairment, and higher rates of hospitalization, psychosis, and suicide attempts. Elevated mood was present in 81.9% of subjects with BP-NOS and 91.8% of subjects with BP-I. Subjects with BP-II had higher rates of comorbid anxiety disorders compared with the other 2 groups and had less functional impairment and lower rates of psychiatric hospitalization than the subjects with BP-I. CONCLUSIONS: Children and adolescents with BP-II and BP-NOS have a phenotype that is on a continuum with that of youth with BP-I. Elevated mood is a common feature of youth with BP-spectrum illness.     

Clinical course of children and adolescents with bipolar spectrum disorders

CONTEXT: Despite the high morbidity associated with bipolar disorder (BP), few studies have prospectively studied the course of this illness in youth. OBJECTIVE: To assess the longitudinal course of BP spectrum disorders (BP-I, BP-II, and not otherwise specified [BP-NOS]) in children and adolescents. DESIGN: Subjects were interviewed, on average, every 9 months for an average of 2 years using the Longitudinal Interval Follow-up Evaluation. SETTING: Outpatient and inpatient units at 3 university centers. PARTICIPANTS: Two hundred sixty-three children and adolescents (mean age, 13 years) with BP-I (n = 152), BP-II (n = 19), and BP-NOS (n = 92). MAIN OUTCOME MEASURES: Rates of recovery and recurrence, weeks with syndromal or subsyndromal mood symptoms, changes in symptoms and polarity, and predictors of outcome. RESULTS: Approximately 70% of subjects with BP recovered from their index episode, and 50% had at least 1 syndromal recurrence, particularly depressive episodes. Analyses of weekly mood symptoms showed that 60% of the follow-up time, subjects had syndromal or subsyndromal symptoms with numerous changes in symptoms and shifts of polarity, and 3% of the time, psychosis. Twenty percent of BP-II subjects converted to BP-I, and 25% of BP-NOS subjects converted to BP-I or BP-II. Early-onset BP, BP-NOS, long duration of mood symptoms, low socioeconomic status, and psychosis were associated with poorer outcomes and rapid mood changes. Secondary analyses comparing BP-I youths with BP-I adults showed that youths significantly more time symptomatic and had more mixed/cycling episodes, mood symptom changes, and polarity switches. CONCLUSIONS: Youths with BP spectrum disorders showed a continuum of BP symptom severity from subsyndromal to full syndromal with frequent mood fluctuations. Results of this study provide preliminary validation for BP-NOS.     

Sources of declarative memory impairment in bipolar disorder: mnemonic processes and clinical features

BACKGROUND: There is mounting evidence that declarative memory processes are impaired in patients with bipolar disorder. However, predictors of the observed impairment are not well understood. This study seeks to: (i) better characterize the nature of declarative memory impairment in bipolar disorder, and (ii) determine the relationship between clinical variables and memory function in bipolar disorder. METHODS: 49 adult patients with bipolar disorder in varying mood states and 38 demographically matched healthy participants completed a comprehensive neurocognitive battery assessing general cognitive functioning, processing speed, and declarative memory. The California verbal learning test was used to characterize learning and memory functions. RESULTS: Although patients with bipolar disorder utilized a similar semantic clustering strategy to healthy controls, they recalled and recognized significantly fewer words than controls, suggesting impaired encoding of verbal information. In contrast, lack of rapid forgetting suggests relative absence of a storage deficit in bipolar patients. While severity of mood symptomatology and illness duration were not associated with task performance, gender and family history significantly affected memory function. CONCLUSIONS: Results suggest that declarative memory impairments in bipolar patients: (1) are consistent with deficits in learning, but do not appear to be related to different organizational strategies during learning, and (2) do not appear to be secondary to clinical state, but rather may be associated with the underlying pathophysiology of the illness.     

Psychosocial disability in the course of bipolar I and II disorders: a prospective, comparative, longitudinal study

CONTEXT: Evidence of psychosocial disability in bipolar disorder is based primarily on bipolar I disorder (BP-I) and does not relate disability to affective symptom severity and polarity or to bipolar II disorder (BP-II). OBJECTIVE: To provide detailed data on psychosocial disability in relation to symptom status during the long-term course of BP-I and BP-II. DESIGN: A naturalistic study with 20 years of prospective, systematic follow-up. SETTING: Inpatient and outpatient treatment facilities at 5 US academic centers.Patients One hundred fifty-eight patients with BP-I and 133 patients with BP-II who were followed up for a mean (SD) of 15 (4.8) years in the National Institute of Mental Health Collaborative Depression Study. MAIN OUTCOME MEASURES: The relationship, by random regression, between Range of Impaired Functioning Tool psychosocial impairment scores and affective symptom status in 1-month periods during the long-term course of illness from 6-month and yearly Longitudinal Interval Follow-up Evaluation interviews. RESULTS: Psychosocial impairment increases significantly with each increment in depressive symptom severity for BP-I and BP-II and with most increments in manic symptom severity for BP-I. Subsyndromal hypomanic symptoms are not disabling in BP-II, and they may even enhance functioning. Depressive symptoms are at least as disabling as manic or hypomanic symptoms at corresponding severity levels and, in some cases, significantly more so. At each level of depressive symptom severity, BP-I and BP-II are equally impairing. When asymptomatic, patients with bipolar disorder have good psychosocial functioning, although it is not as good as that of well controls. CONCLUSIONS: Psychosocial disability fluctuates in parallel with changes in affective symptom severity in BP-I and BP-II. Important findings for clinical management are the following: (1) depressive episodes and symptoms, which dominate the course of BP-I and BP-II, are equal to or more disabling than corresponding levels of manic or hypomanic symptoms; (2) subsyndromal depressive symptoms, but not subsyndromal manic or hypomanic symptoms, are associated with significant impairment; and (3) subsyndromal hypomanic symptoms appear to enhance functioning in BP-II.     

The effect of comorbid anxiety disorder on neuropsychological function in bipolar II disorder

Objectives

Bipolar disorder (BP) is often comorbid with anxiety disorder (ANX), especially in bipolar II disorder (BP-II). BP patients with comorbid ANX often manifest intensified symptoms and harmful dysfunctions. However, most studies have focused on bipolar I disorder (BP-I); few have investigated the effect of comorbid ANX on the neuropsychological function of BP-II patients. We examined neuropsychological functions in BP-II patients with and without comorbid ANX.

Methods

Fifty-nine participants were recruited: 20 patients with interepisode (symptom-free) BP-II without comorbid ANX, 20 with interepisode BP-II with comorbid ANX, and 19 healthy controls. All participants were screened using the Chinese version of the Modified Schedule of Affective Disorder and Schizophrenia-Lifetime (SADS-L). Individuals comorbid with major or minor mental illness other than BP-II were excluded. Comparisons were made between the three groups using neuropsychological tests to assess memory, attention, psychomotor speed, and frontal executive function.

Results

BP-II patients with comorbid ANX showed poorer neuropsychological functions than those in the BP-II-only and control groups. Additionally, BP-II-only patients and controls showed equal cognitive performance.

Conclusions

Because BP-II patients with comorbid ANX had the lowest scores in the majority of neuropsychological functional tests, we conclude that they have greater cognitive impairments than do BP-II patients without comorbid ANX. Neuropsychological dysfunctions seemed more strongly associated with ANX than with BP-II in interepisode periods. Identifying and managing ANX comorbidity is critical when treating BP-II patients.     

Spontaneous and directed application of verbal learning strategies in bipolar disorder and obsessive-compulsive disorder

OBJECTIVES: Individuals with bipolar disorder exhibit neuropsychological impairments when they are euthymic (neither depressed nor manic). One of the most consistently reported cognitive problems in euthymic individuals with bipolar disorder is impairment in verbal episodic memory. Recent findings suggest that episodic memory difficulties in these individuals are attributable to difficulties using organizational strategies during encoding. The purpose of the present study was (i) to investigate whether difficulties using organizational strategies in bipolar disorder are due to a failure in spontaneously initiating verbal organization strategies or are due to difficulties implementing such strategies, and (ii) to compare the characteristics of verbal organizational impairment in bipolar disorder with those observed in individuals with obsessive-compulsive disorder (OCD). METHODS: Study participants were 20 individuals with bipolar I disorder (BP-I), 20 individuals with OCD, and 20 healthy control participants matched for age, gender, and education. Participants completed a verbal encoding paradigm that involved spontaneous and directed use of verbal organization strategies during encoding of word lists. RESULTS: Compared with control subjects, both BP-I and OCD participants showed impaired verbal organization in the spontaneous encoding condition. In the directed encoding condition, OCD patients organized the word lists as well as control participants whereas BP-I participants exhibited lower verbal organization than both control and OCD participants. OCD and BP-I participants' free recall performance did not differ from that of control participants in the spontaneous encoding condition. In the directed encoding condition, BP-I participants recalled fewer words than OCD or control participants. CONCLUSIONS: Episodic memory difficulties in OCD are associated with difficulties spontaneously initiating verbal organization strategies during encoding whereas the ability to implement verbal organization when instructed to do so is preserved. BP-I participants, on the other hand, exhibit difficulties in both spontaneously initiating verbal organization strategies and in the ability to implement such strategies when instructed to do so.     

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.     

Episodic memory impairment in bipolar disorder and obsessive-compulsive disorder: the role of memory strategies

BACKGROUND: There is evidence that individuals with bipolar disorder exhibit neuropsychological impairments not only during mood episodes but also when they are euthymic. One of the most consistently reported cognitive problems in euthymic individuals with bipolar disorder is an impairment in verbal episodic memory. Verbal learning and memory depend on individuals' ability to organize verbal information appropriately during learning. The purpose of the present study was (i) to determine whether episodic memory impairment in euthymic individuals with bipolar disorder is mediated by impairments in organization of verbal information during learning and (ii) to compare the characteristics of memory impairment in bipolar disorder with that previously found in obsessive-compulsive disorder (OCD). METHODS: Study participants were 30 individuals with DSM-IV bipolar I disorder (BP-I), 30 individuals with DSM-IV OCD and 30 normal control participants matched for age, gender and education. Participants completed the California Verbal Learning Test (CVLT), a well-established measure of verbal learning and memory that enables assessment of verbal organization strategies during learning. RESULTS: Compared with control subjects, both BP-I and OCD participants showed impaired performance in long-delayed free recall and verbal organization strategies during learning. BP-I participants showed greater long-delay free recall difficulties but not greater verbal organization difficulties during learning than OCD participants. For OCD participants, the long-delay recall impairment was mediated by difficulties using verbal organizational strategies during learning. In contrast, the group difference in long-delayed free recall between BP-I and control participants remained significant even when semantic clustering was introduced as a mediator. This indicated that BP-I participants' long-delayed free recall difficulties were mediated to a lesser extent by difficulties using verbal organizational strategies than for OCD participants. CONCLUSIONS: Verbal episodic memory problems in individuals with bipolar I disorder and OCD are mediated to different degrees by difficulties using semantic clustering encoding strategies compared with control participants.     

Memory generalization is selectively altered in the psychosis dimension

Global deficits in declarative memory are commonly reported in individuals with schizophrenia and psychotic bipolar disorder, and in their biological relatives. However, it remains unclear whether there are specific components within the global declarative memory dysfunction that are unique to schizophrenia and bipolar disorder, or whether these impairments overlap the two psychoses. This study sought to characterize differential components of learning and memory in individuals within the psychosis dimension: probands with schizophrenia (SZP, n=33), probands with psychotic bipolar I disorder (BDP, n=20), and biological relatives of SZP (SZR, n=21), contrasted with healthy controls (HC, n=26). A computerized cognitive paradigm, the Acquired Equivalence test, with probes for associative learning, memory for learned associations, and memory generalization was administered, along with standardized neuropsychological measures of declarative memory. All study groups were able to learn and remember the associations, although SZP were slower than HC in the initial learning stages. Both SZP (significantly) and BDP (at a trend level) showed altered memory generalization compared to HC (SZP vs. HC, p=.038, d=.8; BDP vs. HC, p=.069, d=.95). SZR showed memory generalization intermediate between SZP and HC, although their performance did not differ significantly from either group. These findings indicate that probands with schizophrenia and bipolar psychoses have similar alteration in the ability to flexibly generalize learned knowledge when probed with novel stimuli, despite overall sufficient associative learning and memory for what they learned. These results suggest that the two disorders present a clinical continuum with overlapping hippocampus-mediated memory generalization dysfunction underlying the psychosis phenotype.     

Neurocognitive function in unaffected first-degree relatives of patients with bipolar disorder: a preliminary report

OBJECTIVE: Patients with remitted bipolar disorder (BD) have persistent impairments in neuropsychological function, particularly in the domains of executive control and declarative memory [Br J Psychiatry 180 (2002) 293]. If these were the phenotypic expression of genetic vulnerability to BD, then healthy subjects with a genetic predisposition to BD would be expected to display the same deficits. This study, therefore, examined neuropsychological function in healthy first-degree relatives of patients with BD. METHOD: A cross-sectional design was employed to compare the performance of 17 unaffected first-degree relatives of BD patients and 17 demographically matched controls on a range of neuropsychological tests. RESULTS: Relatives were significantly impaired on Backward Digit Span, Spatial Span and on tasks of visuospatial declarative memory in comparison with controls. Psychomotor performance and verbal declarative memory were intact, as were non-working memory aspects of executive performance. CONCLUSION: The selective deficits in executive control and declarative memory exhibited by relatives in this study have previously been reported in euthymic BD patients suggesting they may be useful endophenotypic markers of genetic vulnerability to BD.     

Clinical and demographic features of mood disorder subtypes

The aim of this study was to investigate demographic, clinical and symptomatologic features of the following mood disorder subtypes: bipolar disorder I (BP-I); bipolar disorder II (BP-II); major depressive disorder, recurrent (MDR); and major depressive episode, single episode (MDSE). A total of 1832 patients with mood disorders (BP-I=863, BP-II=141, MDR=708, and MDSE=120) were included in our study. The patients were assessed using structured diagnostic interviews and the operational criteria for psychotic illness checklist (n=885), the Hamilton depression rating scale (n=167), and the social adjustment scale (n=305). The BP-I patients were younger; had more hospital admissions; presented a more severe form of symptomatology in terms of psychotic symptoms, disorganization, and atypical features; and showed less insight into their disorder than patients in the other groups. Compared with the major depressive subgroups, BP-I patients were more likely to have an earlier age at onset, an earlier first lifetime psychiatric treatment, and a greater number of illness episodes. BP-II patients had a higher suicide risk than both BP-I and MDSE patients. MDSE patients presented less severe symptomatology, lower age at observation, and a higher number of males. The retrospective approach and the selection constraints due to the inclusion criteria are the main limitations of the study. Our data support the view that BP-I disorder is quite different from the remaining mood disorders from a demographic and clinical perspective, with BP-II disorder having an intermediate position to MDR and MDSE, that is, as a less severe disorder. This finding may help in the search for the biological basis of mood disorders.     

Melancholic outpatient depression in Bipolar-II vs. unipolar

BACKGROUND: DSM-IV melancholic major depressive episode (MDE) in bipolar II disorder (BP-II) is understudied. Study aim was to compare melancholic MDE in BP-II vs. unipolar major depressive disorder (MDD) on diagnostic validators and clinical features. METHODS: Consecutive 39 BP-II and 34 unipolar MDD outpatients in a private practice were interviewed (off psychopharmacotherapy) with the Structured Clinical Interview for DSM-IV, as modified by Benazzi and Akiskal [J. Affect. Disord. 73 (2003) 1], when presenting for treatment of MDE. DSM-IV criteria of melancholic features specifier were followed. Variables studied were index age, gender, age at onset of the first MDE, number of MDE recurrences, severity (measured by GAF, index MDE psychotic features, index MDE symptoms lasting more than 2 years, Axis I comorbidity), index MDE and melancholic symptoms, bipolar family history. Diagnostic validators were onset, family history, course of illness, and clinical picture. RESULTS: BP-II melancholic MDE, vs. MDD melancholic MDE, had significantly lower age at onset and more bipolar family history. Psychomotor agitation was significantly more common in BP-II melancholic MDE, but was present only in 43.5%. Psychomotor retardation was more common in MDD melancholic MDE at a trend level, but was present only in 20.5%. CONCLUSIONS: Psychomotor agitation was more common in BP-II melancholic MDE vs. unipolar MDD, while previous studies on bipolar I (BP-I) had usually found more retardation. The difference could be related to BP-I and BP-II being at least partly distinct disorders. The relatively low frequency of psychomotor change does not seem to support the view that this is the core feature of melancholia. Differences on diagnostic validators (most importantly family history) further support the distinction of melancholic MDE between BP-II and MDD, and support DSM-IV classification.     

Impaired recruitment of the dorsolateral prefrontal cortex and hippocampus during encoding in bipolar disorder.

BACKGROUND: The aim of the present study was to examine the functional neuroanatomy of episodic memory impairment in euthymic subjects with bipolar I disorder. There is evidence that individuals with bipolar disorder have cognitive impairments not only during mood episodes but also when they are euthymic. The most consistently reported cognitive difficulty in euthymic subjects with bipolar disorder is impairment in verbal episodic memory (i.e., the ability to learn new verbal information). METHODS: The current study examined verbal learning in eight euthymic, remitted subjects with bipolar I disorder (BP-I; seven nonmedicated) and eight control subjects matched for age, gender, education, and intelligence. Subjects underwent (15)O-CO(2) positron emission tomography scanning while completing a verbal learning paradigm that consisted of encoding (learning) several lists of words. RESULTS: The BP-I subjects had more difficulties learning the lists of words compared with the control subjects. Compared with control subjects, BP-I subjects exhibited blunted regional cerebral blood flow (rCBF) increases in the left dorsolateral prefrontal cortex (Brodmann's area 9/46) during encoding. CONCLUSIONS: Consistent with previous studies, subjects with BP-I were impaired in learning new verbal information. This was associated with rCBF abnormalities in brain regions involved in learning and episodic memory.     

Neuropsychological functions in bipolar disorders I and II with and without comorbid alcohol dependence

Objective

Bipolar disorder (BP) is a mental disorder most likely to co-occur with substance dependence and abuse, especially alcohol dependence (ALD). Whether the effect of comorbid alcoholism is different between the BP-I and BP-II subtypes remains unclear. We aimed to identify the neuropsychological performance of BP patients with and without comorbid ALD in partial remission from depression or mania, and compare it with that of healthy controls (HCs).

Methods

We recruited 29 HCs and 94 BP patients, whom we categorized into four groups: (1) BP-I without a history of alcohol abuse or dependence (BP-I^− ALD; n = 22), (2) BP-II without a history of alcohol abuse and dependence (BP-II^− ALD; n = 38), (3) BP-I with comorbid ALD (BP-I^+ ALD; n = 16), and (4) BP-II with comorbid ALD (BP-II^+ ALD; n = 18). Only males were recruited in this study.

Results

When patients comorbid with ALD were not excluded, there were no significant differences on neuropsychological tests between the BP-I and BP-II groups. However, when patients with comorbid ALD were excluded, there were significant differences between the two BP^− ALD groups. The BP-I^− ALD group had lower scores on memory subtests (p ≤ 0.01) than the HC and BP-II^− ALD groups, but the BP-II^− ALD and HC groups had similar scores.

Conclusion

We found it important to exclude ALD comorbidity when evaluating neuropsychological functions due to our finding that ALD affected the cognitive performance in BP-I more severely than in the BP-II group. ALD not only impairs neuropsychological function, but also worsen the clinical course and leads to a more pernicious status and negative cycle.     

Evidence for disruption in prefrontal cortical functions in juvenile bipolar disorder

Objectives:  Systematic parsing of executive function processes is critical for the development of more specific models of neurobiological processes mediating disturbed cognition in youth with bipolar disorder (BPD).
Methods:  A sample of 33 children and adolescents with bipolar I disorder (BPD I) (mean age 12.1 ± 3.0 years, 39% female) and 44 demographically matched healthy participants (mean age 12.9 ± 2.8 years, 50% female) completed a neurocognitive battery including measures aimed at detection of disruption in prefrontal cortical circuitry (i.e., working memory, set shifting, and rule attainment).
Results:  Compared to healthy controls, BPD I children exhibited significant deficits in spatial working memory, visual sequencing and scanning, verbal fluency and abstract problem solving, particularly when a memory component was involved. In our spatial delayed response task, memory set size was parametrically varied; the performance pattern in BPD I children suggested deficits in short-term memory encoding and/or storage, rather than capacity limitations in spatial working memory. Earlier age at onset of illness and antipsychotic medication usage were associated with poorer performance on speeded information-processing tasks; however, severity of mood symptomatology and comorbidity with disruptive behavior disorders were not associated with task performance.
Conclusions:  These results suggest impairment in measures of prefrontal cortical function in juvenile BPD I that are similar to those seen in the adult form of the illness, and implicate both the ventral and dorsolateral prefrontal cortex as loci of pathology in juvenile BPD. As these deficits were not associated with clinical state or comorbidity with other disorders, they may reflect trait-related impairments, a hypothesis that will be pursued further in longitudinal studies.     

Evidence for disruption in prefrontal cortical functions in juvenile bipolar disorder

Objectives: Systematic parsing of executive function processes is critical for the development of more specific models of neurobiological processes mediating disturbed cognition in youth with bipolar disorder (BPD). Methods: A sample of 33 children and adolescents with bipolar I disorder (BPD I) (mean age 12.1 ± 3.0 years, 39% female) and 44 demographically matched healthy participants (mean age 12.9 ± 2.8 years, 50% female) completed a neurocognitive battery including measures aimed at detection of disruption in prefrontal cortical circuitry (i.e., working memory, set shifting, and rule attainment). Results: Compared to healthy controls, BPD I children exhibited significant deficits in spatial working memory, visual sequencing and scanning, verbal fluency and abstract problem solving, particularly when a memory component was involved. In our spatial delayed response task, memory set size was parametrically varied; the performance pattern in BPD I children suggested deficits in short‐term memory encoding and/or storage, rather than capacity limitations in spatial working memory. Earlier age at onset of illness and antipsychotic medication usage were associated with poorer performance on speeded information‐processing tasks; however, severity of mood symptomatology and comorbidity with disruptive behavior disorders were not associated with task performance. Conclusions: These results suggest impairment in measures of prefrontal cortical function in juvenile BPD I that are similar to those seen in the adult form of the illness, and implicate both the ventral and dorsolateral prefrontal cortex as loci of pathology in juvenile BPD. As these deficits were not associated with clinical state or comorbidity with other disorders, they may reflect trait‐related impairments, a hypothesis that will be pursued further in longitudinal studies.     

Evidence-based definitions of bipolar-I and bipolar-II disorders among 5,635 patients with major depressive episodes in the Bridge Study: validity and comorbidity

The definitions of bipolar-I (BP-I) and bipolar-II (BP-II) disorders are currently under revision by the APA and by the WHO. We provide evidence of a revised set of criteria for bipolar disorders and major depressive disorder (MDD) which could serve to strengthen the construct and predictive validity of both disorders and enable more incisive studies of treatments and courses of both disorders. In the diagnostic Bridge Study of 5,635 patients with major depressive episodes from 18 countries (Europe, North Africa, Near East and Far East) leading psychiatrists in each country assessed a pre-specified group of symptoms, illness course, family history and duration of episodes; these data allowed tests of several definitions of bipolarity. The primary revised specifier diagnosis of BP-I disorder included manic episodes based on an additional category A criterion (increased activity/energy) and did not apply any exclusion criteria. The revised BP-II disorders included hypomanic episodes of 1–3 days. Family history and illness course validators (history of mania/hypomania among first degree relatives, 2 or more lifetime episodes and first symptoms having occurred before age 30) discriminated clearly between patients with bipolar-I or bipolar-II disorders meeting bipolarity specifier criteria and those with MDD. Specifier definitions provided better discrimination between MDD and the two bipolar subgroups. Patterns of concurrent comorbidities also differed significantly between patients meeting criteria for MDD compared with those meeting bipolar specifier criteria. Comorbidity patterns differed between bipolar-I and bipolar-II patients. This study provides evidence for the validity of modified (specifier) BP-I and BP-II definitions that incorporate illness course and family history which reduce ambiguities of major depressive episodes between bipolar-I and bipolar-II disorders and MDD.     

Organizational and Visual Memory Deficits in Schizophrenia and Bipolar Psychoses Using the Rey-Osterrieth Complex Figure: Effects of Duration of Illness

Verbal declarative memory deficits in schizophrenia are well documented whereas visual declarative memory is less studied. Moreover, there are limited data on whether organizational and visual memory deficits are specific to schizophrenic psychoses. We compared visual memory and organizational function in patients with chronic schizophrenia (n = 79) and chronic bipolar psychotic disorder (n = 14), and in healthy controls (n = 84) using the Rey-Osterrieth Complex Figure (ROCF), testing whether organizational impairments (i.e., executive dysfunctions) account for the visual memory deficit. Groups were comparable on age, handedness and expected intellectual ability (based on single word reading). Using analyses of covariance with sex, parental SES and ethnicity as co-variates, patients with schizophrenia were significantly more impaired than controls on copy accuracy, on recall accuracy, and on percent accuracy of recall. Patients with schizophrenia used a more detail-oriented style on copy and recall and had significantly worse recognition memory. After co-varying IQ, copy organization was also significantly different between the groups. Results for accuracy of copy and recall were not significantly attenuated when controlling for copy organization. Duration of illness was associated with visual memory. Bipolar patients performed at an intermediate level between controls and patients with schizophrenia. The data suggest that in schizophrenia, patients have a visual memory disorder characterized by both organizational processing impairments and retention difficulties, and that there is a decline in visual memory functions with duration of illness. Further research is required to determine whether similar mechanisms underlie the neurocognitive deficits in these psychotic disorders.     

Agitated depression: a valid depression subtype?

PURPOSE: The diagnostic validity of agitated depression (AD, a major depressive episode (MDE) with psychomotor agitation) is unclear. It is not classified in DSM-IV and ICD-10 classification of mental and behavioural disorder (ICD-10). Some data support its subtyping. This study aims to test the subtyping of AD. METHODS: Consecutive 245 bipolar-II (BP-II) and 189 major depressive disorder (MDD) non-tertiary-care MDE outpatients were interviewed (off psychoactive drugs) with Structured Clinical Interview for DSM-IV Axis I Disorders--Clinician Version (SCID-CV), Hypomania Interview Guide (HIGH-C), and Family History Screen. Intra-MDE hypomanic symptoms were systematically assessed. AD was defined as an MDE with psychomotor agitation. Mixed AD was defined as an MDE with four or more hypomanic symptoms (including agitation). FINDINGS: AD was present in 34.7% of patients. AD was mixed in 70.1% of AD patients. AD, vs. non-AD, had significantly (at alpha = 0.05) lower age at onset, more BP-II, females, atypical depressions, bipolar-I (BP-I) and BP-II family history, and was more mixed; racing/crowded thoughts, irritability, more talkativeness, and risky behaviour were significantly more common. Mixed AD, vs. non-AD, had significantly (at alpha = 0.01) lower age at onset, more intra-MDE hypomanic symptoms, BP-II, females, atypical depressions, BP-II family history, and specific hypomanic symptoms (distractibility, racing thoughts, irritable mood, more talkativeness, risky activities). Mixed AD, vs. non-mixed AD, had significantly more intra-MDE hypomanic symptoms (by definition), more recurrences, and more specific hypomanic symptoms (by definition). Non-mixed AD, vs. non-AD, had significantly more intra-MDE hypomanic symptoms and more talkativeness. CONCLUSIONS: AD was common in non-tertiary-care depression outpatients, supporting its diagnostic utility. AD and many bipolar diagnostic validators were associated, supporting its link with the bipolar spectrum. Mixed AD, but not non-mixed AD, had differences vs. non-AD similar to those of AD, suggesting that psychomotor agitation by itself may not be enough to identify AD as a subtype. Findings seem to support the subtyping of mixed AD. This subtyping may have important treatment impact, as antidepressants alone might increase agitation.