Clinical and cognitive factors affecting psychosocial functioning in remitted patients with bipolar disorder.

Impaired interpersonal, social, and occupational functioning is very often observed in patients with bipolar disorder, not only at the acute stages of the illness but in remission as well. This finding raises the question of multiple factors that might affect psychosocial functioning in bipolar patients, such as residual subsyndromal symptoms and neuropsychological deficits. Social cognition impairment, especially impaired Theory of Mind (ToM), might also play an important role in bipolar patients' every-day functioning, similarly to what was found in patients with schizophrenia. The present study aimed to investigate the potential effect of clinical and cognitive factors on the psychosocial functioning of patients with bipolar disorder during remission, assessing ToM along with a broad range of basic cognitive functions. Forty-nine patients with bipolar disorder type I in remission and 53 healthy participants were assessed in general intelligence, working memory, attention, speed processing, verbal learning and memory, and executive functions using a comprehensive battery of neuropsychological tests. The Faux Pas Recognition Test was used to assess ToM. The two groups were matched for gender, age and education level. The Hamilton Rating Scale for Depression (HDRS), the Young Mania Rating Scale (YMRS), and the Brief Psychiatric Rating Scale (BPRS) were also administered to the patients. Every-day functioning was assessed with the Global Assessment of Functioning (GAF). In order to examine the contribution of many factors in psychosocial functioning, we used hierarchical multiple regression analysis. Bipolar patients presented significant impairment compared to healthy participants in all the basic cognitive functions tested with the exception of verbal memory. Moreover, patients had significant poorer performance than healthy controls in overall psyand cognitive ToM but not in affective ToM as measured by Faux Pas. Psychosocial functioning in patient group was significantly correlated to symptom severity-especially depressive (p<0.001) and psychotic symptoms (p=0.001), history of psychotic episodes (p=0.031) and ToM, overall (p=0.001) as well as its cognitive (p=0.023) and affective (p=0.004) components. Only the contribution of ToM in psychosocial functioning remained significant in the final multiple regression model. The findings of the current study indicate that residual symptoms and cognitive dysfunctions, especially deficits in social cognition, negatively affect psychosocial functioning of remitted patients with bipolar disorder. Moreover, our results suggest that ToM may play a central role in these patients' functioning. ToM is a mediator of the relationship between other clinical or cognitive variables and functioning, while it has also significant effect on social skills independently of other factors. Therefore, specific therapeutic interventions targeting social cognitive dysfunction might improve functional outcome in bipolar disorder. Putative contribution of other clinical characteristics (comorbid personality disorders, substance abuse, anxiety) and psychosocial factors (stigma, self-stigma, lack of social network) in bipolar patients' functioning should be examined in future studies.

The relationship of Theory of Mind with symptoms and cognitive impairment in bipolar disorder: a prospective study.

Previous studies in bipolar disorder suggest patients' deficient performance in Theory of Mind tasks, both during manic or depressive episodes and in remission. However, most of the extant studies were cross-sectional and did not control for potential confounders such as residual symptoms or co-existent deficits in other cognitive functions. The present study is the first prospective study that assessed the effect of remission on Theory of Mind (ToM) in patients with Bipolar Disorder (BD) controlling for other cognitive deficits. ToM was assessed in 29 patients with BD type I during an episode of the illness and in remission as well as in 29 healthy controls. The two groups were pair-matched for gender, age and education level. Three tests with different levels of complexity were used to assess ToM: First Order False Belief Task, Hinting Task and Faux Pas Recognition Test. Concomitantly, a comprehensive battery of neuropsychological tests was administered to all participants assessing general intelligence, working memory, attention, speed processing, verbal learning, and memory and executive functions. The Hamilton Rating Scale for Depression, Young Mania Rating Scale, Brief Psychiatric Rating Scale, and GAF were also administered to the patients. Differences between patients--in acute phase and in remission--and the control group on neuropsychological tests were tested using one-way ANOVA with post hoc Bonferroni corrections. The effect of other cognitive deficits on patients' ToM dysfunction was controlled for using general linear models. The patients showed significantly lower performance in all ToM tests during the acute phases as compared to the control group (p values from 0.001 to 0.014). However, these impairments did not persist beyond acute mood episode, except patients' poor performance on Faux Pas (p=0.001). Additionally, patients had poorer performance compared to control group in verbal learning and memory (p<0.001) as well as visuospatial working memory (p<0.001) during both the acute and the euthymic phases of the illness. Patients also had poorer performance than healthy controls in immediate memory (p=0.026) and executive functions (p=0.001), however only during episodes of illness. Differences in Faux Pas did not remain statistically significant when the effect of verbal memory and visuospatial working memory was controlled for. Differences in other ToM tests during episodes did not remain statistically significant, when other cognitive functions that were found impaired in patients during episodes, were controlled for. The findings of this study support the hypothesis that ToM dysfunction in BD is associated with mood symptoms and it might reflect underlying cognitive deficits rather than representing a specific trait marker of the disorder.

[Neurocognitive function in clinically stable patients with schizophrenia or bipolar disorder and normal controls].

There is a substantial body of evidence suggesting that cognitive deficits in schizophrenia (SΖ) and bipolar disorder (BD) persist after the subsidence of active symptoms. However, it is unclear whether the cognitive deficits observed in patients with BD are quantitatively or qualitatively similar to those in SΖ patients. The aim of the study was to assess and compare the cognitive functioning of patients with clinically stable SZ and BD. To the best of our knowledge, this is the first study including a comparison of the Theory of Mind between patients with SZ and BD. General intelligence, attention, speed of processing, working memory, verbal memory and learning, visuospatial ability, executive functions and ToM were assessed in 21 patients with SZ in remission, 23 euthymic BD type I patients, and 27 healthy controls (HC), using WAIS-Vocabulary, Block design, and Digit span, Babcock Story Recall Test, Rey Auditory Verbal Learning Test, Stroop Word-Colour Test, Wisconsin Card Sorting Test, Trail Making Test, and Faux Pas Recognition Test. The three groups were matched for gender, age and education. The SZ and BD groups were also matched in terms of illness duration and the age of the onset of the illness. To be enrolled in the study patients should have been clinically stable for 3 months, operationalized as no change in total Brief Psychiatric Rating Scale, Hamilton Depression Rating Scale (<8), and Young Mania Rating Scale (<6). One-way ANOVA with post hoc Bonferroni corrections was used for the between groups comparisons. Both BD and SC patients were significantly impaired in general intellectual ability, verbal memory and learning, and executive functions compared to HC. Patients with SZ performed significantly worse than patients with BD on verbal memory tasks, whereas BD group did not have significant lower score than SZ in any task. SZ patients performed worse than HC group on attention, processing speed and immediate memory tests, while BD patients on visuospatial ability and working memory. Both SZ and BD groups did not differ from HC regarding Theory of Mind. Our results indicate that stable SZ and euthymic BD exhibit similar profiles of cognitive impairment, consistently with previous studies suggesting that the differences are related to the extent and degree of impairments, rather than being qualitative. Finally, our findings offer support to the hypothesis that the Theory of Mind does not represent a trait marker of schizophrenia or bipolar disorder.

[A volumetric study of brain structures in subtypes of depression].

The aim of this study is to compare the volumes of hippocampus, amygdala and subgenual prefrontal cortex among patients with melancholic depression, patients with psychotic depression and normal controls. Thirty nine patients with a diagnosis of major depression (22 with melancholic and 17 with psychotic subtype) and 18 normal controls were included in the study. Hippocampal, amygdala, anterior and posterior subgenual cortex volumes were measured by manual tracings on magnetic resonance volumetric images and compared across the 3 groups. We identified larger amygdala volumes and smaller left anterior subgenual cortex volumes in both patient groups compared to controls. There were no differences in hippocampal, right anterior and posterior subgenual cortex volumes across the 3 groups. In conclusion, melancholic and psychotic depression were not differentiated regarding the volumes of the hippocampus, the amygdala, and anterior and posterior subgenual cortex, even though amygdala volumes and left anterior subgenual cortex volume of both patient groups were differentiated compared to controls.

Contrasting patterns of deficits in visuospatial memory and executive function in patients with major depression with and without ECT referral.

BACKGROUND: The pretreatment neuropsychological profile of drug-resistant patients with major depressive disorder (MDD) referred for electroconvulsive therapy (ECT) may differ from that of their drug-respondent MDD counterparts. Such differences could help in identifying distinct MDD subtypes, thus offering insights into the neuropathology underlying differential treatment responses. METHOD: Depressed patients with ECT referral (ECTs), depressed patients with no ECT referral (NECTs) and non-psychiatric Controls (matched groups, n=15) were assessed with memory and executive function tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB). RESULTS: ECTs scored significantly lower than NECTs in the Mini-Mental State Examination (MMSE; p=0.01). NECTs performed worse than Controls in the Paired Associates Learning (PAL) task (p<0.03; Control/NECT p<0.01) and the Spatial Recognition Memory (SRM) task (p<0.05; Controls/NECTs p<0.05); ECTs performed between Controls and NECTs, not differing from either. In the Intra/Extradimensional (IED) set-shifting task, ECTs performed worse that Controls and NECTS (IED: p<0.01; Controls/ECTs p<0.01), particularly in the shift phases, which suggests reduced attentional flexibility. In Stockings of Cambridge (SOC), ECTs abandoned the test early more often than Controls and NECTs (H=11, p<0.01) but ECTs who completed SOC performed comparably to the other two groups. CONCLUSIONS: A double dissociation emerged from the comparison of cognitive profiles of ECT and NECT patients. ECTs showed executive deficits, particularly in attentional flexibility, but mild deficits in tests of visuospatial memory. NECTs presented the opposite pattern. This suggests predominantly frontostriatal involvement in ECT versus temporal involvement in NECT depressives.

Mental pain and suicide risk: application of the Greek version of the Mental Pain and the Tolerance of Mental Pain scale.

According to Shneidman's theory, mental pain or "psychache", which refers to an endopsychic painful experience consisted of excessively felt negative feelings, is a key component to the understanding of suicidal behaviour, as to its psychological features. Shneidman himself supported that 'suicide is caused by psychache', more precisely suicide occurs when a person can no longer tolerate this pain. Findings of previous studies have shown that mental pain is an independent predictive factor for suicidal behaviour. In the present study we evaluated the psychometric properties of the Greek version of the Mental Pain Scale (MPS) and the Tolerance for Mental Pain Scale (TMPS) ina non clinical sample consisted of 112 participants (73 female and 39 male). Moreover, we explore the relationships between mental pain, depression, and suicide risk and for the first time the effect of the tolerance for mental pain on depression and suicide risk. We hypothesized that both the level of mental pain and the degree of tolerance for mental pain would predict suicide risk, independently of the level of depression. Both MPS and TMPS appear to have satisfactory to high levels of internal consistency, test-retest reliability, and concurrent validity. Suicide risk was correlated to mental pain, tolerance for mental pain, and depression. Multiple regression analysis showed that mental pain and tolerance for mental pain have a significant contribution to suicide risk, independently of depression, confirming our hypothesis.Using an additional multivariate regression with the factors extracted from MPS and TMPS as independent variables, we found that especially 'loss of control' of mental pain and the ability to 'contain the pain' contribute uniquely to suicide risk. Our findings offer support to the hypothesis that mental pain is a clinical entity distinct from depression with a specific and important contribution to the suicide risk.Depression alone is not enough to cause suicide. The mental pain construct, although related to depression,could shed light on the comprehension of the human experience that leads to suicide. Relieving mental pain may constitute a distinct and important treatment goal, along with the remission of depression and despair, so that the person can maintain control and contain all the distressing events that comprise the painful experience. Both MPS and TMPS appear to be valid and reliable tools for the assessment of mental pain and its tolerance, respectively. They could also be employed in further investigation on the role of specific aspects of the mental pain experience in suicidal behaviours.

Neuropsychological relationships in paranoid schizophrenia with and without delusional misidentification syndromes. A comparative study.

Delusional misidentification syndromes (DMSs) and schizophrenia are strongly associated, since the former occur predominantly in the context of paranoid schizophrenia. However, the possible underlying neuropsychological relationships between DMSs and paranoid schizophrenia have not been thoroughly investigated. The aim of the present study was to investigate whether DMSs in paranoid schizophrenia are associated with a distinct neuropsychological substrate indicative of differential bilateral frontal and right hemisphere dysfunction. We compared two matched groups of paranoid schizophrenic patients with (N=22) and without (N=22) DMS(s) on a battery of neuropsychological tests assessing mainly frontal and right hemisphere functions. No statistically significant differences were detected between the two groups. Our findings are indicative of a bilateral frontal and right hemisphere dysfunction of equal severity in both DMS and non-DMS patients with paranoid schizophrenia.

Psychotic (delusional) major depression in late life: a clinical study.

BACKGROUND: Psychotic (delusional) major depression (PMD) in the elderly is a common condition in inpatient settings. There is evidence that late age onset depressives are more likely to be psychotic. OBJECTIVES: The aim of this study was to investigate the frequency, sociodemographic, and clinical characteristics of PMD in hospitalized elderly depressives. METHODS: The sample consisted of 118 elderly patients consecutively admitted at three different clinics. All patients fulfilled DSM-IV criteria for major depression disorder and were diagnosed on the basis of Structured Clinical Interview for DSM-IV (SCID). The subjects were also assessed using the Hamilton Rating Scale for Depression, the Mini Mental State Examination (MMSE) and a physical health rating scale. RESULTS: PMD was positively associated with age of depression onset over 60 [corrected]. The PMD patients were also more severely depressed, more psychomotorically retarded and referred more past psychotic depressive episodes. Furthermore, age at onset influenced the type of delusions, so that PMD patients with age [corrected] over 60 at onset expressed delusions of hypochondriacal and nihilistic content more frequently. CONCLUSIONS: The results of our study demonstrated that PMD in the elderly has a later age at onset.

Dopamine receptor responsivity in schizophrenic patients in a drug-free state and after treatment with olanzapine.

1. Olanzapine is a novel atypical antipsychotic with affinity for a number of neurotransmitter receptors including dopamine D1, D2, D4, serotonin 5HT2A, 5HT2C, histamine H1, a1-adrenergic, and muscarinic receptors. 2. A neuroendocrinological method to check the degree of dopamine receptor blocking is by measuring the prolactin (PRL) responses to acute (i.m.) administration of haloperidol (HAL). The authors applied this test in a group of male patients with DSM-IV schizophrenia in the drug-free state. The patients were subsequently treated with olanzapine (OLZ) (mean daily dose: 22.5+/-5.8) and the test was repeated six weeks later. For the HAL-test, 5mg HAL were injected i.m. and blood samples were taken at times 0, 30, 60, 90 and 120 minutes. Fourteen patients enrolled in the study. Psychopathology was assessed by means of the Brief Psychiatric Rating Scale (BPRS). 3. Six weeks treatment with OLZ resulted in significant decreases in the total BPRS score and on the score of its subscales for positive, negative, and general psychopathology. Comparison of the PRL response patterns, after HAL administration by analysis of variance for repeated measures (ANOVAR) for drug treatment and time, revealed a highly significant time effect (F=28.98, p=0.000) and a significant treatment by time interaction (F=8.27, p=0.000008). Namely, in the drug-free state significant increases were found in the PRL levels after i.m. HAL administration which were significantly reduced during treatment with OLZ, indicating moderate receptor blockade.

Clinical subtypes of schizophrenic disorders: a cluster analytic study.

Two hundred and fifty-five psychiatric inpatients with a definite diagnosis of DSM-IV schizophrenic disorder were examined by means of the Structured Clinical Interview and rated on the 30 main items of the Positive and Negative Syndrome Scale (PANSS). Patients' scores were subjected to a cluster analysis, using Ward's method. Cluster analysis indicated the existence of five groups. The first group (n = 46) comprised patients with overall psychopathology of minimal severity, the second group (n = 39) patients with severe positive symptoms along with symptoms of psychomotor excitement, the third group (n = 58) patients with severe positive psychopathology only, the fourth group (n = 34) patients with severe positive negative depressive and cognitive symptoms and, finally, the fifth group (n = 78) patients with severe negative symptoms only. Patients in the first and third groups were older and their illnesses were of longer duration compared to those of the remaining groups. With respect to DSM-IV clinical types of schizophrenic disorders, the paranoid type predominated in the second and the third groups, whereas the disorganized and catatonic types were markedly overpresented in the fifth group.

Clinical features of delusional beliefs in schizophrenic and unipolar mood disorders: a comparative study.

We assessed comparatively 13 clinical features of delusions in a sample of 132 deluded inpatients of both sexes with schizophrenic (n = 89) or unipolar mood disorders (n = 43). Patients with schizophrenic disorders exhibited higher levels of severity than those with unipolar depression with respect to the features of vagueness-illogicality, bizarreness, systematization, conviction, duration and affective incongruence, whereas the reverse held true with respect to the feature of emotional impact. Furthermore, the two diagnostic groups were compared to each other with respect to patients' scores on five dimensions of their delusions obtained through factor analysis, namely emotional and behavioral impact, cognitive disintegration, delusional certainty, volitional dyscontrol and affective inappropriateness. Schizophrenic patients exhibited higher levels of severity than depressives on the second and fifth dimensions, whereas the reverse held true with respect to the fourth one. Our results suggest that particular features of delusions as well as broader dimensions thereof, may assist in the differential diagnosis of unipolar depression with psychotic features from schizophrenic disorders.

Five-factor model of schizophrenic psychopathology: how valid is it?

Aim of the study was to examine the consistency of the five-factor model of schizophrenic symptoms, assess its validity and evaluate its dimensional factor structure using confirmatory factor (CFA) analysis. A sample of 258 randomly assigned DSM-III R patients with schizophrenic disorders were studied by means of the structured clinical interview for the Greek validated Positive and Negative Syndrome Scale (PANSS) and were rated on its 30 items. Patients' scores were subjected to principal component analysis (PCA) with varimax rotation. Internal consistency for each of the components was determined by the use of Cronbach's alpha. External validity of the model derived was investigated by searching for possible relationships between the components and sociodemographic characteristics with the aid of canonical correlation analysis. Confirmatory factor analysis (CFA) was also performed. Using the scree plot criterion PCA revealed a five-factor model. These factors were interpreted as representing--in a decreasing order of relative importance--the following dimensions of schizophrenic psychopathology: negative, excitement, depression, positive and cognitive impairment. The model was comparable with six previous factor analytic studies. Internal consistency was quite satisfactory whereas external validity was found to be not so powerful. CFA did not show that the proposed model yields an adequate factor structure.

Clinical dimensions of delusional beliefs: a factor-analytic study.

We investigated the factorial composition as well as the demographic, anamnestic and clinical correlates of 13 features of delusional beliefs in a sample of 127 psychiatric inpatients with active delusions at the time of their assessment: Six factors were extracted, jointly accounting for 67.3% of the variance, which were interpreted as the dimensions of cognitive disintegration, volitional dyscontrol, doxastic strength, distress, incongruence and expansiveness, respectively. Moreover, most factors exhibited distinctive profiles of demographic, anamnestic or clinical correlates. Overall, our findings provide supportive evidence for both the clinical multidimensionality of delusional beliefs at the factor-analytic level and the - at least partial - external validity of the factorial solution obtained.

Prolactin secretion in response to haloperidol challenge in delusional (psychotic) and non-delusional depression.

Certain studies on measures related to central neurotransmitter activity have demonstrated that in delusional (psychotic) depression there is a dopaminergic dysregulation which distinguishes it from non-psychotic depression. A neuroendocrinologic method to check the degree of DA receptor responsivity is by measuring the prolactin responses to acute intramuscular administration of haloperidol. We studied this possibility by applying the haloperidol test in seven delusional and ten non-delusional depressed patients. All patients met DSM-IV criteria for a major depressive episode, single or recurrent, with or without psychotic features. After a three-week washout period, 5 mg of haloperidol were injected i.m. and blood samples were taken at 0, 30, 60, 90 and 120 minutes. In both trials, significant time effects were observed (elevated prolactin levels, F = 11.36, P = 0.000). However, the prolactin responses to haloperidol did not differ significantly between the two patient groups (F = 0.12, P = 0.97). These data do not show a difference in D(2) receptor responsivity, at least at the hypothalamus-pituitary level, between psychotic and non-psychotic depression.

Clinical homogeneity of DSM-IV schizophrenic disorders.

We investigated the lifetime fulfillment of five subcriteria of diagnostic criterion A in 94 inpatients with a definite diagnosis of DSM-IV schizophrenic disorder. Among the five diagnostic features captured by criterion A, only delusions were found to be almost universal, whereas of the remaining four, only hallucinations and negative symptoms occurred in more than half of all the cases. Overall, almost 60% of the 28 possible patterns of combination among the five subcriteria were found to be fulfilled although 60% of the cases were accounted for by only 4 patterns, which were also identified by means of a cluster analysis, as accounting for the totality of the cases. The first cluster was characterized by the fulfillment of subcriteria 1,2 and 5, the second by subcriteria 1 and 2, the third by subcriteria 1 and 5 and the fourth by subcriteria 1,2, and 3. The substantial clinical heterogeneity of the DSM-IV category of schizophrenic disorders with respect to their diagnostically characteristic features captured in criterion A is traced to the polythetic character of its five subcriteria.

Gabapentin as monotherapy in the treatment of acute mania.

Two cases of mania treated with gabapentin, a new anticonvulsant, are presented. After 2 weeks of treatment a moderate improvement of both patients was observed. The antimanic effect of gabapentin awaits confirmation by systematic, well designed studies.

Neurochemical variables in schizophrenic patients during switching from neuroleptics to clozapine.

1. The study aimed to search for the effect of clozapine on the levels of the main metabolites of dopamine homovanillic acid (HVA), serotonin 5-hydroxyindoleacetic acid (5-HIAA) and norepinephrine 3-methoxy-4-hydroxyphenylglycol (MHPG) in urine as well as on plasma levels of HVA, 5-HIAA, prolactin (PRL) and cortisol. 2. Seventeen male patients diagnosed as suffering from DSM-IIIR schizophrenia completed the study. 3. The patients were switched from classical antipsychotics to clozapine. After six weeks treatment with clozapine the severity of psychopathology (total BPRS score) decreased significantly (p = 0.00004). pHVA and -5-HIAA did not change significantly. uMHPG increased significantly (p = 0.017). Both PRL and cortisol levels decreased significantly (p = 0.0002, p = 0.032 respectively). Patients with high HVA levels in both plasma and urine at baseline had a lower BPRS score at the end of treatment period (p = 0.0001, p = 0.049 respectively).

Beck Depression Inventory in the detection of depression among neurological inpatients.

The validity of the Beck Depression Inventory (BDI) was assessed in a group of 150 neurological inpatients using Receiver Operating Characteristic analysis and DSM-III-R as external criterion. As regards depressive disorders as a whole, it was found that the best trade-off between sensitivity and specificity was the cutoff score of 20. The discriminating ability of the BDI for major depressive disorder was quite satisfactory at the cutoff score of 29 contrary to the dysthymic disorder in which the discriminating power of the BDI was not acceptable. In conclusion, the use of the BDI in neurological settings is useful with cutoff scores depending on the research purposes.

Comorbidity of dsm-iii-r personality disorders in schizophrenic and unipolar mood disorders: a comparative study.

We investigated the overall prevalence and the differential comorbidity of Diagnostic and Statistical Manual (DSM)-III-R personality disorders in 166 remitted or recovered patients with schizophrenic (n = 102) or unipolar mood disorder (n = 64). Over 60% of both patient groups met the DSM-III-R criteria of at least one DSM-III-R personality disorder as assessed by means of the Structured Clinical Interview for DSM-III-R (SCID-II-R), receiving on average 3.1 personality diagnoses. Neither DSM-III-R categories of personality disorders, nor scores on its three clusters A, B and C, nor total score on SCID-II-R differed significantly across the two groups. In conclusion, DSM-III-R personality disorders, although highly prevalent in schizophrenic and unipolar mood disorders, lack any specificity with respect to these categories of mental disorders.