History Of Psychotic Features Research Articles

Relationship of Hair Cortisol with History of Psychosis, Neuropsychological Performance and Functioning in Remitted Later-Life Major Depression

Introduction: Major depressive disorder (MDD) is associated with hypothalamic-pituitary-adrenal axis dysfunction that may persist into remission. Preliminary evidence suggests that this dysfunction may be associated with impaired neuropsychological performance in remitted MDD. MDD with psychotic features (“psychotic depression”) is associated with greater neuropsychological and functional impairment than nonpsychotic depression, including in remission. Therefore, the aim of this exploratory study was to examine the relationships among hair cortisol concentration (HCC) – a marker of longer term endogenous cortisol exposure – and history of psychotic features, neuropsychological performance, and functioning in remitted MDD. Methods: This cross-sectional study compared the relationship between HCC and (i) history of psychosis, (ii) neuropsychological performance, and (iii) everyday functioning in a group of 60 participants with remitted later-life MDD using Pearson’s correlation coefficients. This study also measured HCC in a group of 36 nonpsychiatric volunteers to examine the clinical significance of HCC in the patient group. Results: There were no statistically significant correlations between HCC and history of psychotic features, neuropsychological performance, or functioning. Furthermore, there was no clinically meaningful difference in HCC between patients and nonpsychiatric volunteers. Conclusion: This study is the first to examine HCC in psychotic depression. The results do not support the hypothesis that impaired neuropsychological performance, and everyday function in remitted psychotic depression is due to a sustained elevation of cortisol.

Relationships Among History of Psychosis, Cognition and Functioning in Later-Life Remitted Major Depression

ObjectiveThis study tested the hypotheses that, in older adults with remitted major depression, a history of psychotic features and poorer neuropsychological performance would be independently associated with poorer everyday functioning, but that neuropsychological performance would explain more of the variance in functioning than history of psychotic features. MethodsThis cross-sectional study included 73 patients aged 50 years or older with remitted psychotic major depression or nonpsychotic major depression. The dependent variables were subjective and objective measures of function. The independent variables were history of psychotic features during one or more major depressive episodes in the previous 10 years and neuropsychological performance. Linear regression models examined the association of independent variables with function, controlling for pertinent covariates. Effect sizes were calculated for the magnitude of difference in function between the patient participants and an age- and gender-matched nonpsychiatric group, and distribution of functioning scores were compared between groups. ResultsIn separate models, history of psychotic features and poorer processing speed, executive function, and verbal learning were independently associated with poorer participant-reported functioning and performance-based functioning. However, the association of psychotic features with functioning was no longer statistically significant when tested in the same models as neuropsychological measures. Effect sizes of the difference in functioning between patients and the nonpsychiatric group were significantly larger for the remitted psychotic than the remitted nonpsychotic depression group; functioning scores were more heterogeneous in the remitted psychotic depression group. ConclusionPatients with remitted psychotic depression exhibit greater, and clinically important, impairment in everyday functioning than those with remitted nonpsychotic depression. Neuropsychological impairment appears to contribute to this relationship.

Bipolar disorder with and without a history of psychotic features: fMRI correlates of sustained attention

Bipolar disorder with and without a history of psychotic features: fMRI correlates of sustained attention

RELATIONSHIP OF HAIR CORTISOL CONCENTRATION WITH HISTORY OF PSYCHOSIS, NEUROPSYCHOLOGICAL PERFORMANCE, AND EVERYDAY FUNCTIONING IN REMITTED LATER-LIFE MAJOR DEPRESSIVE DISORDER

Introduction Psychotic features are more prevalent in older adults with depression than in younger depressed adults. Psychotic major depressive disorder (PMD) is associated with poorer neuropsychological performance and poorer everyday functioning, in both acute and remitted states, compared with non-psychotic major depressive disorder (NPMD). In addition, PMD is also associated with more pronounced dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, including elevated cortisol levels, but it is not known whether this difference between PMD and NPMD persists in remission. The goal of this exploratory study was to test the hypothesis that a history of psychotic features, poorer neuropsychological performance, and poorer everyday functioning were associated with higher cortisol levels in sustained remission of major depressive disorder. If confirmed, it could suggest a possible mechanism for neuropsychological and functional impairment in remitted PMD. In order to examine the relationship between sustained HPA dysfunction in remission and the aforementioned variables, we measured hair cortisol concentration (HCC), a measure of longer-term cortisol exposure. Methods This study used a cross-sectional design and included 60 participants aged 50 years or older with a history of major depressive disorder (n = 17 with NPMD and n = 43 with PMD) in sustained remission and 36 non-psychiatric comparison participants. Hair samples were collected using standardized methods and cortisol concentrations were determined from the first 3-cm hair segment most proximal to the scalp, or from as much hair as was available for participants with shorter hair. This hair segment represents the hair growth over the 3-month period prior to the sampling. HCC was measured in a research laboratory with extensive experience in this analysis using a validated high sensitivity enzyme immunoassay (EIA) that is standard in the field. In order to examine the relationships between HCC and i) history of psychotic features, ii) neuropsychological performance (processing speed, executive function, and verbal memory), and iii) everyday functioning (participant-report general functioning and observer-rated IADL performance), we performed three sets of correlation analyses, one for each variable of interest (point biserial for psychosis history and HCC; Pearson's r for neuropsychological and functional measures). We calculated effect sizes and 95% confidence limits in order to compare HCC results between patient and non-psychiatric comparison groups. HCC data were highly skewed and were log transformed for all analyses. Results NPMD and PMD groups had mean (SD) HCCs of 18.86 (32.97) pg/mg and 12.48 (11.26) pg/mg, respectively. The correlation between HCC and history of psychosis was weak (r = -0.02), as were the correlations between HCC and the neuropsychological measures (r ranging between -0.11 and 0.1). The correlations between HCC and i) IADL performance (r = -0.04) and ii) general functioning (r = -0.074) were also weak. None of these correlations were statistically significant. The mean (SD) HCC for non-psychiatric comparison subjects was 13.86 (20.06) pg/mg. Both effect sizes for the difference between the clinical and non-psychiatric comparison groups were small (0.26 for NPMD versus Comparison group and 0.25 for PMD versus Comparison group). Conclusions This is the first study to assess HCC in PMD and to examine the relationship between HCC and cognition and between HCC and everyday functioning in MDD. We did not find a correlation between HCC and history of psychosis, neuropsychological performance, or functioning in later-life patients with MDD in sustained remission. Further, there was no substantial difference in mean HCC between the patient and non-psychiatric comparison group. There is variability in the literature regarding HCC in MDD and regarding the relationship between HPA-axis function and neuropsychological performance in remitted MDD. Our findings will be discussed in this context. This research was funded by This study was funded by a research grant from the University Health Network Centre for Mental Health ($14,000)

THE ASSOCIATIONS AMONG HISTORY OF PSYCHOSIS, NEUROPSYCHOLOGICAL PERFORMANCE, AND FUNCTIONING IN REMITTED LATER-LIFE MAJOR DEPRESSION

Introduction Observational studies report that people with psychotic major depressive disorder (PMD) have poorer functional outcome than those with non-psychotic major depression (NPMD), but this finding could be explained by less robust recovery and residual symptoms in PMD. In addition, neuropsychological performance is worse in those with PMD than NPMD, both acutely and in remission. The aim of this study was to examine the relative contributions of a history of psychosis and neuropsychological performance to impaired everyday function in patients with remitted later-life major depressive disorder (MDD). We hypothesized that, in later-life patients with MDD, a history of psychotic features and poorer neuropsychological function would be independently associated with poorer everyday functioning, but that poorer neuropsychological performance would be more strongly associated with poorer functioning compared to history of psychosis. In order to place the results in a broader context, we examined everyday functioning in an age- and gender-matched non-psychiatric comparison group. Methods This cross-sectional design study included 73 patients aged 50 years and older with a history of MDD (n = 51 with NPMD and n = 22 with PMD) in sustained remission and 42 non-psychiatric comparison subjects. Sociodemographic, clinical, neuropsychological, and functional data were collected by an investigator blind to the history of psychotic features. Everyday functioning, the dependent variable, was divided into general functioning (measured by participant-report) and IADL performance (measured by observer-rated assessment). The independent variables were i) history of psychosis and ii) neuropsychological performance in the domains of processing speed, memory, and executive function. Relationships between each independent variable and functioning were analyzed using multiple linear regression models. The relative contribution of history of psychosis and neuropsychological performance to functioning was analyzed using multiple regression models with history of psychosis entered in the first step and the neuropsychological variable in the second step. All models included covariates that were potential confounders. We also calculated effect sizes for the difference in functioning between MDD and non-psychiatric comparison participants. Results Patients with PMD exhibited substantial deficits in measures of processing speed and, to a lesser extent, executive function, compared to NPMD patients and to population norms. History of psychosis was independently related to poorer IADL performance (β = 0.262, t = 3.03, p = 0.004) and general functioning (β = -0.29, t = -2.46, p = 0.017). Poorer performance on measures of processing speed (β = -0.468, t = -4.99, p In comparison to non-psychiatric subjects, the effect size of functional impairment in patients with remitted PMD was large (Cohen's d for IADL function = 0.80; Cohen's d for general functioning = 0.97), whereas the impairment was small to moderate in remitted NPMD (Cohen's d for IADL function = 0.10; Cohen's d for general functioning = 0.64). Conclusions Later-life remitted PMD is associated with poorer everyday functioning compared to NPMD, with clinically-significant deficits. However, this relationship is no longer significant when neuropsychological function, especially processing speed, is accounted for. This study advances previous literature by including only patients with rigorously-defined sustained remission and measuring functioning comprehensively using both participant-report and performance-based measures. We will discuss future directions of these research findings, including examining neurobiological correlates of processing speed deficits in remitted PMD. This research was funded by This study was funded by the University Health Network Centre for Mental Health's research grant ($14,000)

Effects of childhood trauma on adult moral decision-making: Clinical correlates and insights from bipolar disorder

BackgroundChildhood adversity has been shown to exert profound effects on basic psychological processes well into adulthood. Some of these processes, such as those related to reward and emotion, play critical roles in moral decision-making. As a population with high rates of childhood trauma as well as heterogenous clinical presentation, individuals with bipolar disorder (BD) constitute an enriched group in which to examine the correlates of trauma and other clinical variables with moral cognition. Methods62 euthymic BD patients and 27 controls responded to moral dilemma scenarios and completed the Childhood Trauma Questionnaire. ResultsResults revealed a main effect of diagnosis on moral decision-making only when both personal force and an intention were required, indicating a more utilitarian style in BD patients relative to controls. Several interesting patterns also emerged regardless of diagnostic status. Higher ratings of physical neglect were significantly associated with higher ratings of acceptability (a utilitarian tendency) across dilemma types, and a similar pattern was observed at the trend level for experiences of emotional neglect. Significant main effects on moral decision-making were also observed for sex, illness duration, and history of psychotic features in the BD sample. LimitationsThe present study is limited by the self-reported nature of the CTQ and by the small number of trials of moral dilemmas. In addition, practical and clinical implications of the moral dilemmas paradigm are limited due to its abstract nature. ConclusionsOur results indicate that certain clinical features as well as childhood maltreatment (in particular neglect) may significantly impact moral decision making in adult life. Surprisingly, childhood trauma was associated with a more utilitarian style, which is in the opposite direction from previous effects shown in PTSD. Although speculative, our results suggest that there may be a protective quality associated with utilitarian moral decision-making tendencies.

Auditory processing deficits in bipolar disorder with and without a history of psychotic features.

Auditory perception deficits have been identified in schizophrenia (SZ) and linked to dysfunction in the auditory cortex. Given that psychotic symptoms, including auditory hallucinations, are also seen in bipolar disorder (BD), it may be that individuals with BD who also exhibit psychotic symptoms demonstrate a similar impairment in auditory perception. Fifty individuals with SZ, 30 individuals with bipolar I disorder with a history of psychosis (BD+), 28 individuals with bipolar I disorder with no history of psychotic features (BD-), and 29 normal controls (NC) were administered a tone discrimination task and an emotion recognition task. Mixed-model analyses of covariance with planned comparisons indicated that individuals with BD+ performed at a level that was intermediate between those with BD- and those with SZ on the more difficult condition of the tone discrimination task and on the auditory condition of the emotion recognition task. There were no differences between the BD+ and BD- groups on the visual or auditory-visual affect recognition conditions. Regression analyses indicated that performance on the tone discrimination task predicted performance on all conditions of the emotion recognition task. Auditory hallucinations in BD+ were not related to performance on either task. Our findings suggested that, although deficits in frequency discrimination and emotion recognition are more severe in SZ, these impairments extend to BD+. Although our results did not support the idea that auditory hallucinations may be related to these deficits, they indicated that basic auditory deficits may be a marker for psychosis, regardless of SZ or BD diagnosis.

Paternal age effect: Replication in schizophrenia with intriguing dissociation between bipolar with and without psychosis.

Advanced paternal age (APA) is a risk factor for schizophrenia (Sz) and bipolar disorder (BP). Putative mechanisms include heritable genetic factors, de novo mutations, and epigenetic mechanisms. Few studies have explored phenotypic features associated with APA. The Genomic Psychiatry Cohort established a clinically characterized repository of genomic samples from subjects with a Sz-BP diagnosis or unaffected controls, 12,975 with parental age information. We estimated relative risk ratios for Sz, schizoaffective depressed and bipolar types (SA-D, SA-B), and BP with and without history of psychotic features (PF) relative to the control group, comparing each paternal age group to the reference group 20-24 years. All tests were two-sided with adjustment for multiple comparisons. Subjects with fathers age 45+ had significantly higher risk for all diagnoses except for BP w/o PF. APA also bore no significant relation to family psychiatric history. In conclusion, we replicated APA as a risk factor for Sz. To our knowledge, this is the first published report of APA in a BP sample stratified by psychosis history, extending this association only in BP w/PF. This suggests that phenotypic expression of the APA effect in Sz-BP spectrum is psychosis, per se, rather than other aspects of these complex disorders. The lack of a significant relationship between paternal age and familial disease patterns suggests that underlying mechanisms of the paternal age effect may involve a complex interaction of heritable and non-heritable factors. The authors discuss implications and testable hypotheses, starting with a focus on genetic mechanisms and endophenotypic expressions of dopaminergic function. © 2015 Wiley Periodicals, Inc.

Basal ganglia and thalamic morphology in schizophrenia and bipolar disorder

In this study, we examined the morphology of the basal ganglia and thalamus in bipolar disorder (BP), schizophrenia-spectrum disorders (SCZ-S), and healthy controls (HC) with particular interest in differences related to the absence or presence of psychosis. Volumetric and shape analyses of the basal ganglia and thalamus were performed in 33 BP individuals [12 without history of psychotic features (NPBP) and 21 with history of psychotic features (PBP)], 32 SCZ-S individuals [28 with SCZ and 4 with schizoaffective disorder], and 27 HC using FreeSurfer-initiated large deformation diffeomorphic metric mapping. Significant volume differences were found in the caudate and globus pallidus, with volumes smallest in the NPBP group. Shape abnormalities showing inward deformation of superior regions of the caudate were observed in BP (and especially in NPBP) compared with HC. Shape differences were also found in the globus pallidus and putamen when comparing BP and SCZ-S groups. No significant differences were seen in the nucleus accumbens and thalamus. In summary, structural abnormalities in the caudate and globus pallidus are present in BP and SCZ-S. Differences were more apparent in the NPBP subgroup. The findings herein highlight the potential importance of separately examining BP subgroups in neuroimaging studies.

A Multicenter Tractography Study of Deep White Matter Tracts in Bipolar I Disorder

Tractography studies investigating white matter (WM) abnormalities in patients with bipolar disorder have yielded heterogeneous results owing to small sample sizes. The small size limits their generalizability, a critical issue for neuroimaging studies of biomarkers of bipolar I disorder (BPI). To study WM abnormalities using whole-brain tractography in a large international multicenter sample of BPI patients and to compare these alterations between patients with or without a history of psychotic features during mood episodes. A cross-sectional, multicenter, international, Q-ball imaging tractography study comparing 118 BPI patients and 86 healthy control individuals. In addition, among the patient group, we compared those with and without a history of psychotic features. University hospitals in France, Germany, and the United States contributed participants. Participants underwent assessment using the Diagnostic Interview for Genetic Studies at the French sites or the Structured Clinical Interview for DSM-IV at the German and US sites. Diffusion-weighted magnetic resonance images were acquired using the same acquisition parameters and scanning hardware at each site. We reconstructed 22 known deep WM tracts using Q-ball imaging tractography and an automatized segmentation technique. Generalized fractional anisotropy values along each reconstructed WM tract. Compared with controls, BPI patients had significant reductions in mean generalized fractional anisotropy values along the body and the splenium of the corpus callosum, the left cingulum, and the anterior part of the left arcuate fasciculus when controlling for age, sex, and acquisition site (corrected for multiple testing). Patients with a history of psychotic features had a lower mean generalized fractional anisotropy value than those without along the body of the corpus callosum (corrected for multiple testing). In this multicenter sample, BPI patients had reduced WM integrity in interhemispheric, limbic, and arcuate WM tracts. Interhemispheric pathways are more disrupted in patients with than in those without psychotic symptoms. Together these results highlight the existence of an anatomic disconnectivity in BPI and further underscore a role for interhemispheric disconnectivity in the pathophysiological features of psychosis in BPI.

Cerebrospinal fluid kynurenic acid is associated with manic and psychotic features in patients with bipolar I disorder

Kynurenic acid (KYNA), an end metabolite of tryptophan degradation, antagonizes glutamatergic and cholinergic receptors in the brain. Recently, we reported elevated levels of cerebrospinal fluid (CSF) KYNA in male patients with bipolar disorder. Here, we investigate the relationship between symptomatology and the concentration of CSF KYNA in patients with bipolar I disorder. CSF KYNA levels from euthymic male {n = 21; mean age: 41 years [standard deviation (SD) = 14]} and female [n = 34; mean age: 37 years (SD = 14)] patients diagnosed with bipolar I disorder were analyzed using high-performance liquid chromatography (HPLC). Euthymic bipolar I disorder patients with a lifetime occurrence of psychotic features had higher CSF levels of KYNA {2.0 nm [standard error of the mean (SEM) = 0.2]; n = 43} compared to patients without any history of psychotic features [1.3 nm (SEM = 0.2); n = 12] (p = 0.01). Logistic regression, with age as covariate, similarly showed an association between a history of psychotic features and CSF KYNA levels [n = 55; odds ratio (OR) = 4.9, p = 0.03]. Further, having had a recent manic episode (within the previous year) was also associated with CSF KYNA adjusted for age (n = 34; OR = 4.4, p = 0.03), and the association remained significant when adjusting for a lifetime history of psychotic features (OR = 4.1, p = 0.05). Although the causality needs to be determined, the ability of KYNA to influence dopamine transmission and behavior, along with previous reports showing increased brain levels of the compound in patients with schizophrenia and bipolar disorder, may indicate a possible pathophysiological role of KYNA in the development of manic or psychotic symptoms.

Relational memory in psychotic bipolar disorder

Recent research has highlighted the phenotypic and genetic overlap of bipolar disorder and schizophrenia. Cognitive deficits in bipolar disorder parallel those seen in schizophrenia, particularly for bipolar disorder patients with a history of psychotic features. Here we explored whether relational memory deficits, which are prominent in schizophrenia, are also present in patients with psychotic bipolar disorder. We tested 25 patients with psychotic bipolar disorder on a relational memory paradigm previously employed to quantify deficits in schizophrenia. During the training, participants learned to associate a set of faces and background scenes. During the testing, participants viewed a single background overlaid by three trained faces and were asked to recall the matching face, which was either present (Match trials) or absent (Non-Match trials). Explicit recognition and eye-movement data were collected and compared to those for 28 schizophrenia patients and 27 healthy subjects from a previously published dataset. Contrary to our prediction, we found psychotic bipolar disorder patients were less impaired in relational memory than schizophrenia subjects. Bipolar disorder subjects showed eye-movement behavior similar to healthy controls, whereas schizophrenia subjects were impaired relative to both groups. However, bipolar disorder patients with current delusions and/or hallucinations were more impaired than bipolar disorder patients not currently experiencing these symptoms. We found that patients with psychotic bipolar disorder had better relational memory performance than schizophrenia patients, indicating that a history of psychotic symptoms does not lead to a significant relational memory deficit.

Relationships between auditory event‐related potentials and mood state, medication, and comorbid psychiatric illness in patients with bipolar disorder

Patients with bipolar disorder (BD) exhibit aberrations in auditory event-related potentials (ERPs), although the relationships between these measures and mood state at testing, comorbid psychiatric illness, presence of psychotic features, and medication usage are unclear. The purpose of this study was to investigate the relationships between these factors and auditory ERP measures in BD patients. An auditory 'oddball' discrimination task was used to elicit ERPs from 69 patients with type I BD and 52 healthy controls. Patients were placed into subgroups based upon their mood state at testing (euthymic or symptomatic), and ANOVA was used to compare amplitude and peak latency measures from the N100, P200, N200, and P300 ERP components across subgroups. Multiple regression was used to investigate relationships between ERP measures and comorbid psychiatric diagnosis, history of psychotic features, and medication status. Relative to healthy control participants, euthymic and symptomatic BD patients exhibited reduced P300 and P200 amplitude, but ERP measures did not differ among BD patients on the basis of mood status. A history of a comorbid anxiety disorder was associated with reduced N200 peak latency, but prolonged P300 peak latency among BD patients. No other relationships between clinical variables and ERP measures were significant. The results suggest that disrupted auditory attention may be observed in BD patients regardless of their mood state at testing, medication status, or history of psychosis. These results extend previous findings, and provide further evidence for aberrations in the P300 ERP as an endophenotype for BD.

Should Bipolar Medication Be Halted During Pregnancy?

Should Bipolar Medication Be Halted During Pregnancy?

A survey of prescribing practice of antipsychotic maintenance treatment for manic-depressive outpatients

Survey questionnaires were mailed to public hospital psychiatrists practising in a French region to obtain information on the manic-depressive outpatients they personally followed up. Data were collected on 222 manic-depressive outpatients managed by 43 separate psychiatrists. More than two thirds were receiving at least one antipsychotic, and 17% were prescribed a depot-neuroleptic. Predictors of antipsychotic prescription were a history of psychotic features ( OR = 3.4; 95%CI 1.7–6.9), early age at onset ( OR = 2.1; 95%CI 1.0–4.8) and low educational level ( OR = 3.1; 95%CI 1.5–6.3). Similar predictors were found for depot-neuroleptic prescription. Although these indicate that the prescription of antipsychotic for manic-depressive outpatients is not random, only 14% of patients were receiving mood stabilizers only. Owing to the potential side effects of antipsychotics, the benefit-to-risk ratio of antipsychotic use in the maintenance treatment of manic-depressive patients has to be carefully taken into account.

Alternative Prophylactic Treatments to Lithium in Bipolar Disorders

The research literature on alternative drug treatments to lithium therapy for the prevention of recurrences in bipolar disorders is discussed. In particular, the data on anticonvulsants (carbamazepine and valproic acid), antidepressants (alprazolam), and calcium channel blockers (verapamil) are reviewed and original data on clonazepam (CLN) are reported. In a preliminary study on six patients with bipolar disorders (DSM-III-R) without a history of psychotic features in which lithium prophylaxis was ineffective, contraindicated, or badly tolerated, CLN was administered in combination with low-dose neuroleptics or antidepressants in all but one case. All subjects were followed for 13 to 34 months. There were no relapses during the observation period with CLN dose regimens ranging from 1.5-8 mg/day p.o. Side effects were minimal and mostly consisted of transient sedation.