Neuropsychological testing of cognitive impairment in euthymic bipolar disorder: an individual patient data meta-analysis.

OBJECTIVE: An association between bipolar disorder and cognitive impairment has repeatedly been described, even for euthymic patients. Findings are inconsistent both across primary studies and previous meta-analyses. This study reanalysed 31 primary data sets as a single large sample (N = 2876) to provide a more definitive view. METHOD: Individual patient and control data were obtained from original authors for 11 measures from four common neuropsychological tests: California or Rey Verbal Learning Task (VLT), Trail Making Test (TMT), Digit Span and/or Wisconsin Card Sorting Task. RESULTS: Impairments were found for all 11 test-measures in the bipolar group after controlling for age, IQ and gender (Ps ≤ 0.001, E.S. = 0.26-0.63). Residual mood symptoms confound this result but cannot account for the effect sizes found. Impairments also seem unrelated to drug treatment. Some test-measures were weakly correlated with illness severity measures suggesting that some impairments may track illness progression. CONCLUSION: This reanalysis supports VLT, Digit Span and TMT as robust measures of cognitive impairments in bipolar disorder patients. The heterogeneity of some test results explains previous differences in meta-analyses. Better controlling for confounds suggests deficits may be smaller than previously reported but should be tracked longitudinally across illness progression and treatment.

Functional MRI of sustained attention in bipolar mania.

We examined sustained attention deficits in bipolar disorder and associated changes in brain activation assessed by functional magnetic resonance imaging (fMRI). We hypothesized that relative to healthy participants, those with mania or mixed mania would (1) exhibit incremental decrements in sustained attention over time, (2) overactivate brain regions required for emotional processing and (3) progressively underactivate attentional regions of prefrontal cortex. Fifty participants with manic/mixed bipolar disorder (BP group) and 34 healthy comparison subjects (HC group) received an fMRI scan while performing a 15-min continuous performance task (CPT). The data were divided into three consecutive 5-min vigilance periods to analyze sustained attention. Composite brain activation maps indicated that both groups activated dorsal and ventral regions of an anterior-limbic network, but the BP group exhibited less activation over time relative to baseline. Consistent with hypotheses 1 and 2, the BP group showed a marginally greater behavioral CPT sustained attention decrement and more bilateral amygdala activation than the HC group, respectively. Instead of differential activation in prefrontal cortex over time, as predicted in hypothesis 3, the BP group progressively decreased activation in subcortical regions of striatum and thalamus relative to the HC group. These results suggest that regional activation decrements in dorsolateral prefrontal cortex accompany sustained attention decrements in both bipolar and healthy individuals. Stable amygdala overactivation across prolonged vigils may interfere with sustained attention and exacerbate attentional deficits in bipolar disorder. Differential striatal and thalamic deactivation in bipolar disorder is interpreted as a loss of amygdala (emotional brain) modulation by the ventrolateral prefrontal-subcortical circuit, which interferes with attentional maintenance.

The influence of religious affiliation on time to first treatment and hospitalization.

UNLABELLED: Longer duration of untreated psychosis (DUP) has been associated with treatment-refractory illness, significant cognitive decline, and poorer long-term outcomes. There are many factors, including social and cultural, that promote longer DUP. To date, there have been no studies to evaluate religion's effect on DUP. In this study, we evaluated the effect of certain religious affiliations and degree of religious practice on the DUP. METHODS: A total of 195 patients were recruited aged 18 to 45 years with the presence of at least 1 psychotic symptom (delusions, hallucinations, or prominent thought disorder). Patients were evaluated on their religious practice prior to the index episode using a Likert-style scale. Using a similar scale, patients were asked about their religious affiliation categorized as Catholic, Protestant, or neither. RESULTS: Correlational analysis revealed that the time to first treatment and time to first hospitalization were both was negatively related to degree of religious practice (r = -0.15, N = 161, p < 0.05 and r = -0.18, N = 161, p < 0.05, respectively). Between-group comparisons revealed longer DUP in the Protestant group compared to the no affiliation and Catholic groups (p = 0.05). CONCLUSION: From our results, it appears that the degree of religious practice does not affect length of time to treatment in psychotic patients. However, having a Protestant religious affiliation is strongly associated with having a greater delay in treatment seeking for psychosis. Factors contributing to a longer DUP in this group warrant further study.

Reaction time measures of sustained attention differentiate bipolar disorder from schizophrenia.

Although continuous performance tasks (CPTs) are becoming more common in psychiatric research, it remains unclear which performance measures best differentiate psychiatric patient groups and along which psychological dimensions. To address this the authors examined sustained attention decrements in patients with bipolar disorder and schizophrenia using CPT measures of perceptual sensitivity, response bias, and psychomotor processing speed. Patients with bipolar disorder with psychotic features (N=20), schizophrenia (N=20), and healthy controls (N=20) were evaluated using structured clinical interviews. These patients were rated with the Scale for the Assessment of Positive Symptoms and the Young Mania Rating Scale before completing a degraded-stimulus version of the CPT. Psychomotor processing speed was the only measure that reliably differentiated the groups across the entire vigilance period and was the strongest predictor of group membership. These findings suggest that reaction time measures may be sensitive to differences in the sustained attention abilities of patients with bipolar disorder and schizophrenia. By incorporating reaction time measures into CPT assessments, discriminant ability may be enhanced.

Frequency and severity of religious delusions in Christian patients with psychosis.

The influence of religious activity on the severity of religious delusions is unclear. This study examined whether Catholic and Protestant patients experienced more religious delusions than non-religiously affiliated patients. We also explored whether the severity of religious delusions, according to the Religious Delusions item on the Scale for the Assessment of Positive Symptoms (SAPS), was associated with the amount of religious activity. The Protestants experienced more religious delusions than Catholics and those without religious affiliation. Although when the groups were combined, patients who were more religiously active experienced more severe religious delusions (n=133), there was no difference in the severity of religious delusions across the non-religious, Catholic and Protestant groups. Religious affiliation may influence the frequency of religious delusions, particularly in Protestant individuals, but religious affiliation appears to be independent of religious delusion severity.

Persistent attentional dysfunction in remitted bipolar disorder.

OBJECTIVES: Although previous research has shown that attentional dysfunction is common during acute mood episodes in individuals with bipolar disorder (BPD), few studies have examined whether attentional deficits are evident during periods of symptom stability. The goal of this study was to determine whether clinically stable individuals with BPD would have attentional disturbances relative to healthy subjects. METHODS: Fourteen patients with BPD and 12 healthy comparison subjects participated in the study, and were administered the Degraded Stimulus Continuous Performance Test (DSCPT), Digit Span Distractibility Test (DSDT) and Grooved Pegboard Test (GPT). Psychiatric symptoms were assessed with the Young Mania Rating Scale and the Scale for the Assessment of Positive Symptoms. Medication side effects were measured with the Simpson Rating Scale. RESULTS: The patient group responded significantly more slowly than the control group on the DSCPT (z = -2.52, p = 0.01) and the GPT (z = -3.37, p = 0.001). There was a trend towards the BPD patients demonstrating impaired perceptual sensitivity on the DSCPT (z = 1.68, p = 0.09). The two groups did not differ on the DSDT (z = -1.06, p = 0.3). Poor performance on the GPT and DSCPT target reaction time were not associated with symptom ratings or medications. CONCLUSION: The findings suggest that impairments in fine motor skills and reaction time may be present in clinically stable patients with BPD, even after accounting for psychiatric symptoms and medication effects. Performance decrements on attentional tasks may be in part reflective of motor impairments in patients with BPD.

Is impaired outcome following a first manic episode due to mood-incongruent psychosis?

BACKGROUND: Mood-incongruent psychosis during the course of bipolar disorder has been associated with poor outcome. However, it remains unknown whether this is secondary to persistent affective or psychotic symptoms or both. METHOD: Fifty patients with bipolar disorder between the ages of 16 and 45 years were recruited during their first psychiatric hospitalization for mania. These patients were evaluated using structured and semi-structured clinical instruments then followed longitudinally. Outcomes during the first eight months of follow-up were compared between patients with mood-incongruent psychosis and those without (i.e., patients with mood-congruent psychosis or no psychosis) during the index manic episode. Specifically, ratings of the percent of weeks during follow-up with psychosis and affective syndromes and symptoms, as well as ratings of global outcome (GAF), were compared. RESULTS: Patients with mood-incongruent psychosis at the index hospitalization exhibited significantly more weeks during follow-up with both mood-incongruent and mood-congruent psychotic symptoms than patients without mood-incongruent psychosis. Mood-incongruent psychosis was also associated with poorer overall functioning during the outcome interval. The groups did not differ in the percent of weeks with affective syndromes or symptoms. Treatment during follow-up did not differ between groups and was not associated with outcome variables in general. CONCLUSION: Mood-incongruent psychosis that occurs during the first manic episode appears to predict an increased likelihood of persistent psychotic symptoms during the subsequent eight months. This persistence of psychosis is associated with a worse overall course of illness as compared to patients without mood-incongruent psychosis. LIMITATIONS: These results apply to a relatively short outcome period and are from a single center.

The impact of substance abuse on the course of bipolar disorder.

BACKGROUND: Substance abuse occurs at high rates in bipolar disorder. The reasons for this co-occurrence are unknown. Alcohol use disorders have been associated with both earlier and later age of onset of bipolar disorder, in part based on the temporal associations of the two conditions. Both drug and alcohol use disorders are associated with impaired outcome of bipolar illness. This influence may involve both direct effects of alcohol or drugs on the initiation of affective symptoms and indirect effects on treatment compliance. To extend these previous findings we examined the temporal associations of substance abuse and affective symptoms in patients with new onset bipolar disorder. METHODS: Associations between affective symptoms and alcohol and cannabis use disorder symptoms were evaluated using regression and time-series correlative methods in 50 new-onset bipolar patients. RESULTS: The duration of alcohol abuse during follow-up was associated with the time patients experienced depression. The duration of cannabis abuse was associated with the duration of mania. Several subgroups could be identified with different temporal relationships among these disorders. CONCLUSIONS: Although the relationships among substance use and bipolar disorders are complex, systematic study of the courses of the disorders might clarify how these conditions interact longitudinally. As the numbers of subjects in specific subgroups are relatively small in this study, these results should be considered preliminary.

Eight-month functional outcome from mania following a first psychiatric hospitalization.

The aim of this study was to identify how different areas of function (role performance, interpersonal relationships, sexual activity and recreational enjoyment) differentially recover from a manic episode during the 8 months following a first psychiatric hospitalization. Fifty patients with bipolar disorder, 16-45 years of age, who met the criteria for a current manic episode were recruited during their first psychiatric hospitalization. Forty-two (84%) of these participated in follow-up. Patients were evaluated using structured and semi-structured clinical instruments and the four areas of functional outcome were assessed with the LIFE interview. Recovery of the four areas of function were compared using survival and correlational analyses. Logistic regression identified factors associated with functional outcome. The four aspects of function were not significantly intercorrelated at baseline or during follow-up. Moreover, the survival curves for the different areas of function significantly differed. Specifically, patients demonstrated better recovery of sexual activity and worse recovery of recreational enjoyment than the other areas of function. Different clinical and demographic variables predicted recovery of the different areas of function. In conclusion, following a first manic episode, recovery of psychosocial function can be divided into separate components, i.e., role function, interpersonal relationships, sexual activity and recreational enjoyment, that appear to be relatively independent. Further clarification of recovery of these different areas of function may lead to better integrated treatments that maximize functional improvement early in the course of bipolar disorder.

Directed forgetting deficits in patients with temporal lobe epilepsy: an information processing perspective.

Although mesial temporal lobe brain damage is frequently associated with memory loss, it is unclear whether the deficit results entirely from a disruption in the processing of relevant information or whether it also reflects interference from irrelevant information. Directed forgetting is one procedure that can be used, along with standard tests of memory, to investigate this distinction. Seventeen patients with a diagnosis of complex-partial seizures of temporal lobe origin and 17 healthy volunteers were compared on lexical decision, free recall, and recognition tests in a directed-forgetting paradigm. These tests created a memory profile to measure the influence of task relevant and irrelevant information in implicit and explicit memory. Compared with healthy volunteers, the patients were significantly impaired on the memory tasks overall [F(5,25) = 5.01, p < .01]. Specifically, directed forgetting in lexical decision and recognition both discriminated between the groups [stepdown F(1,26) = 6.84, eta 2 = .26, p < .05 and stepdown F(1,25) = 5.36, eta 2 = .13, p < .05, respectively]. The results suggest that interictal memory performance in temporal lobe epilepsy may be disrupted in part because of a deficit in the differential processing of task relevant and task irrelevant information, particularly at retrieval.