Cortisol to Dehydroepiandrosterone Sulphate Ratio and Executive Function in Bipolar Disorder.

INTRODUCTION: Bipolar disorder (BD) is associated with impairment in cognitive domains such as verbal memory and executive functions. Very few studies have assessed dehydroepiandrosterone sulphate (DHEA-S) in BD and its relation to cognitive functioning despite evidence showing its regulatory effects on glucocorticoid action. The aim of our study was to explore the association of cortisol, DHEA-S, and cortisol to DHEA-S ratio with visuospatial memory and executive functioning in BD. METHODS: Cognitive performance of 60 bipolar I patients and 30 healthy subjects was evaluated by using Cambridge Neuropsychological Test Automated Battery tasks targeting visuospatial memory (spatial recognition memory) and executive functions (planning [Stockings of Cambridge; SOC] and attentional set shifting [ID/ED]). Morning serum cortisol and DHEA-S levels were measured in patients. Main effects of cortisol, DHEA-S, and cortisol/DHEA-S ratio for each neurocognitive task were explored in multiple regression analyses correcting for demographic and clinical parameters as well as treatment-related factors (current use of antipsychotic and mood stabilizer medication). RESULTS: Bipolar patients showed poorer performance than healthy subjects in planning and attentional set shifting but not in visuospatial memory. Cortisol to DHEA-S ratio predicted worse performance in planning (SOC). CONCLUSIONS: This is the first study to assess memory and executive function in BD in relation to DHEA-S and cortisol to DHEA-S ratio. We report an association of cortisol to DHEA-S ratio with worse performance in planning in bipolar I patients, which warrants further investigation.

Guilt Delusional Beliefs Increase the Risk of Suicidal Attempt in Elderly Unipolar Psychotic Depressives.

The aim of this study was to investigate the differential effect of various delusion categories, namely, guilt, paranoid, impending disaster, and somatic on suicidal attempts in elderly patients experiencing unipolar psychotic major depression (PMD), because the evidence on this is scarce. The sample consisted of 65 consecutively admitted patients 60 years or older, experiencing PMD, and assessed by means of Structured Clinical Interview for DSM-4 (Patient Edition), Hamilton Depression Rating Scale, Mini-Mental Status Examination (MMSE), and by a physical impairment rating scale. Patients with guilt delusional beliefs had 5.31 times higher odds (95% confidence interval, 1.37-25.40) of a suicidal attempt than the patients without guilt delusional beliefs, controlling for sex, age, prior history of suicide attempt, MMSE, and hallucinations. In addition, 17 PMD patients with lifetime suicidal attempt compared with 48 PMD patients without lifetime suicidal attempt presented only higher age of disorder onset (p = 0.008). Of the four categories of delusions assessed, only guilt delusions were associated with an increased risk for suicidal attempt.

Psychotic (delusional) depression and completed suicide: a systematic review and meta-analysis.

BACKGROUND: It remains unclear whether psychotic features increase the risk of completed suicides in unipolar depression. The present systematic review coupled with a meta-analysis attempts to elucidate whether unipolar psychotic major depression (PMD) compared to non-PMD presents higher rates of suicides. METHODS: A systematic search was conducted in Scopus, PubMed, and "gray literature" for all studies providing data on completed suicides in PMD compared to non-PMD, and the findings were then subjected to meta-analysis. All articles were independently extracted by two authors using predefined data fields. RESULTS: Nine studies with 33,873 patients, among them 828 suicides, met our inclusion criteria. PMD compared to non-PMD presented a higher lifetime risk of completed suicides with fixed-effect pooled OR 1.21 (95% CI 1.04-1.40). In a sub-analysis excluding a very large study (weight = 86.62%), and comparing 681 PMD to 2106 non-PMD patients, an even higher pooled OR was found [fixed-effect OR 1.69 (95% CI 1.16-2.45)]. Our meta-analysis may provide evidence that the presence of psychosis increases the risk of suicide in patients suffering from severe depression. The data are inconclusive on the contribution of age, mood congruence, comorbidity, and suicide method on PMD's suicide risk. The lack of accurate diagnosis at the time of suicide, PMD's diagnostic instability, and the use of ICD-10 criteria constitute the main study limitations. CONCLUSIONS: The presence of psychosis in major depression should alert clinicians for the increased risk of completed suicide. Thus, the implementation of an effective treatment both for psychotic depression and patients' suicidality constitutes a supreme priority.

Clinical and treatment-related predictors of cognition in bipolar disorder: focus on visual paired associative learning.

Bipolar disorder (BD) is associated with impairment in cognitive domains such as verbal memory and executive functions. However, visual paired associative learning (PAL) has been far less researched. Neurocognitive dysfunction in BD patients has been related to several clinical factors, but data on the effect of medication are relatively scarce and inconsistent. The aim of our study was to explore the effect of clinical and treatment-related parameters on executive functions and visual memory/learning, including PAL, in BD. Cognitive performance of 60 bipolar I patients and 30 healthy subjects was evaluated by using CANTAB battery tasks targeting spatial recognition memory, PAL and executive functions (set shifting, planning, inhibitory control). Bipolar patients showed poorer performance in PAL, set shifting, planning and inhibitory control than healthy subjects; however, only differences in PAL and planning survived correction for multiple comparisons. Number of previous manic episodes and illness duration predicted worse performance in set shifting and PAL, respectively, whereas current treatment with valproate predicted better performance in PAL. This is one of the first studies to assess clinical and treatment-related predictors of PAL in BD. We report a possibly beneficial effect of valproate on PAL, which warrants further investigation.

Primary polydipsia: a case report.

Primary polydipsia (PP) is etiologically associated with physical factors and psychiatric disorders ("psychogenic polydipsia"). We present the case of a 28-year-old man with severe symptoms of polydipsia and polyuria. After a comprehensive physical assessment, the only finding was a lesion suggestive of pituitary microadenoma in the magnetic resonance imaging (MRI) scan of the brain. A thorough clinical and diagnostic assessment and the administration of a wide range of psychometric tools revealed no major psychiatric disorder apart from chronic anxiety and mild depressive symptoms. Our patient's PP symptoms might be associated with a dysfunction of the thirst center, which is located closely to the neuroanatomical lesion found in the MRI scan. Given that the underlying pathophysiology of PP remains, to a large extent, unclear, we emphasize on the difficulties to distinguish between PP's subtypes.

A case of autophagia: a man who was mutilating his fingers by biting them.

Self-mutilating behaviors could be minor and benign, but more severe cases are usually associated with psychiatric disorders or with acquired nervous system lesions and could be life-threatening. The patient was a 66-year-old man who had been mutilating his fingers for 6 years. This behavior started as serious nail biting and continued as severe finger mutilation (by biting), resulting in loss of the terminal phalanges of all fingers in both hands. On admission, he complained only about insomnia. The electromyography showed severe peripheral nerve damage in both hands and feet caused by severe diabetic neuropathy. Cognitive decline was not established (Mini Mental State Examination score, 28), although the computed tomographic scan revealed serious brain atrophy. He was given a diagnosis of impulse control disorder not otherwise specified. His impulsive biting improved markedly when low doses of haloperidol (1.5 mg/day) were added to fluoxetine (80 mg/day). In our patient's case, self-mutilating behavior was associated with severe diabetic neuropathy, impulsivity, and social isolation. The administration of a combination of an antipsychotic and an antidepressant proved to be beneficial.

Differential association of cortisol with visual memory/learning and executive function in Bipolar Disorder.

The association of cortisol with cognition has been understudied in Bipolar Disorder (BD); available evidence is inconsistent while it is unknown whether cortisol's effects vary across neurocognitive domains implicating different brain structures. This study aimed to examine the association of cortisol with two cognitive tasks targeting visual memory and executive function (planning) in BD, related to the hippocampus and prefrontal lobe, respectively. Cambridge Neuropsychological Test Automated Battery (CANTAB) tasks targeting paired associative learning (PAL) and planning (Stockings of Cambridge; SOC) were administered to 60 BD type I patients. Basal serum cortisol was also measured. Higher cortisol was associated with worse performance in PAL, but not SOC, after controlling for gender, education, illness duration and treatment with mood stabilizers. This is the first study to examine the association of cortisol with neurocognitive function in BD while controlling for clinicodemographic and treatment-related factors. We found a significant association of cortisol with hippocampal-related visual memory/learning but not with prefrontal lobe-related executive function, suggesting domain-specific underlying mechanisms of cognitive dysfunction in BD. Future studies should further explore cortisol's brain structure-specific effects on cognitive functioning in BD.

Similar or Different Neuropsychological Profiles? Only Set Shifting Differentiates Women With Bipolar vs. Borderline Personality Disorder.

There is ongoing debate about the similarities and differences between bipolar disorder (BD) and borderline personality disorder (BPD). Very few studies have concurrently assessed their neuropsychological profile and only on a narrow array of neuropsychological tests. We aimed to investigate the differences of these two patient groups on visual memory, executive function, and response inhibition. Twenty-nine BD patients, 27 BPD patients and 22 controls (all female) were directly compared on paired associates learning (PAL), set shifting (ID/ED), problem solving (SOC), and response inhibition (SSRT) using Cambridge Neuropsychological Test Automated Battery (CANTAB). Rank-normalized outcomes were contrasted in one-way ANOVA tests. Discriminant analysis was finally performed to predict BD or BPD patient status. BD patients performed significantly worse than controls on all tasks. BPD patients performed significantly worse than HC on all tests except SST. Significant differences between the two patient groups were recorded only on ID/ED, where BPD patients performed worse (p = 0.044). A forward stepwise discriminant analysis model based on ID/ED and SOC predicted correctly patients' group at 67.9% of cases. In conclusion, BD and BPD female patients appear to be more similar than different as regards their neuropsychological functions. This study is the first to show that BPD patients display more deficits than BD patients when directly compared on the set shifting executive function test, a marker of cognitive flexibility. Discerning BD from BPD patients through neuropsychological performance is promising but would improve by using additional subtler tests and psychometric evaluation.

Suicidal ideation during COVID-19 lockdown in Greece: Prevalence in the community, risk and protective factors.

The aim of this study was to investigate the prevalence of suicidal ideation in the community as well as the risk and protective factors of suicidal ideation during restriction measures in Greece, after the outbreak of the COVID-19 pandemic. Α web-based anonymous survey was conducted during the first lockdown period. Participants completed the Generalized Anxiety Disorder scale (GAD-2), the Patient Health Questionnaire (PHQ-2), the Systemic Clinical Outcome and Routine Evaluation (SCORE-15), the Connor-Davidson Resilience Scale (CD-RISK-2), and a self-report questionnaire for COVID-19 pandemic-related data. From a total of 5,116 adults included in the study, 5.20% reported suicidal thoughts, 14.17% were potential clinical cases of anxiety, and 26.51% of depression. Participants presented significantly higher suicidal ideation rates during the last two weeks of the lockdown compared to its previous two weeks. Unmarried or divorced marital status, mental health history, poor perceived quality of physical health, impaired family functioning, anxiety and depression symptoms were independently associated with higher odds of suicidal ideation, whereas higher resilience, positive feelings with regard to the lockdown measures, relationship with friends, and faith in a Supreme Being were associated with lower suicidal ideation odds. According to the findings, suicidal ideation prevalence might be considered elevated and its increase during the lockdown period alarming. The risk and protective factors identified in the study offer valuable information for the development of preventive strategies against suicidal ideation, especially in times of crisis.

Extrapyramidal side effects and suicidal ideation under fluoxetine treatment: a case report.

BACKGROUND: We present the case of a 52-year-old woman with depression who developed extrapyramidal symptoms (mainly parkinsonism) and suicidal ideation while on fluoxetine. METHODS: The patient underwent neurological and neuroimaging examination. RESULTS: The patient's neurological and neuroimaging examinations were normal and there was no other cause of extrapyramidal symptoms. The patient showed remission of the aforementioned symptomatology when fluoxetine was discontinued. CONCLUSIONS: This case shows that fluoxetine can be associated with extrapyramidal symptoms, and this may have an aggravating affect on clinical depression progress and the emergence of suicidal ideation.

Pituitary volume in unaffected relatives of patients with schizophrenia and bipolar disorder.

BACKGROUND: Hypothalamic-pituitary-adrenal (HPA) axis hyperactivity has been demonstrated in both schizophrenia and bipolar disorder, but the mechanisms underlying this abnormality are still unclear. Enlarged pituitary volume has been recently reported in patients with first episode psychosis and been interpreted as a consequence of an increased activation of the HPA axis. The aim of this study was to assess the contribution of familial liability to pituitary volume in schizophrenia and bipolar disorder. Pituitary volume may be an indirect measure of HPA axis activity. METHODS: MRI brain scans and measurements of pituitary volumes were obtained for 183 subjects: 26 patients with established schizophrenia or schizoaffective disorder, 44 of their unaffected first-degree relatives (22 familial schizophrenia, 22 non-familial schizophrenia), 29 patients with established bipolar disorder, 38 of their unaffected first-degree relatives, and 46 healthy comparison subjects. RESULTS: We found a significantly larger pituitary volume (effect size=0.7) in unaffected relatives of patients with schizophrenia compared with controls (p=0.002); the pituitary was even larger in relatives of patients with familial schizophrenia (effect size=0.8, p=0.005). We did not find a significant difference in pituitary volume when comparing the relatives of bipolar patients with controls. Among patients, those with schizophrenia who were receiving prolactin-elevating antipsychotics had an increased pituitary volume compared with controls (effect size=1.0, p=0.006). CONCLUSIONS: These results suggest that the larger pituitary volume previously reported in first episode schizophrenia could be partly due to a genetic susceptibility to over-activate the HPA axis.

Sex-related variation of neurocognitive functioning in bipolar disorder: Focus on visual memory and associative learning.

Bipolar disorder (BD) is associated with cognitive deficits in attention, verbal memory and executive functions. However, only few studies have examined sex effects on cognition despite their clinical relevance. Given that visual memory/ learning has been understudied the aim of our study was to investigate sex-related variation in cognition (executive functions and visual memory/ learning) in BD. Cognitive performance of 60 bipolar-I patients and 30 healthy controls was evaluated by using CANTAB battery tasks targeting spatial memory (SRM), paired associative learning (PAL) and executive functions. We fitted a multivariate analysis of covariance (MANCOVA), followed by task-specific ANCOVAs. A significant diagnosis by sex interaction effect was detected (MANCOVA); specifically, diagnosis-specific sex effects were found for SRM and PAL, as healthy males outperformed healthy females but this pattern was attenuated in BD patients. Patients' clinicodemographic characteristics, current psychopathology or medication status did not differ across sexes and were, therefore, unlikely to explain detected sex effects. Our study is one of few studies to assess sex-related variation in cognition in BD and the first to record a diagnosis-specific sex effect for two tasks of visuo-spatial memory/ learning, indicating that sex-related variation in healthy subjects is disrupted in BD.

Assessment of cerebral blood volume in schizophrenia: A magnetic resonance imaging study.

Brain atrophy has consistently been observed in schizophrenia, representing a 'gross' evidence of anatomical abnormalities. Reduced cerebral blood volume (CBV) may accompany brain size decrement in schizophrenia, as suggested by prior small SPECT studies. In this study, we non-invasively investigated the hemisphere CBV in a large sample of patients suffering from schizophrenia with perfusion-weighted imaging (PWI). PWI images were obtained, following intravenous injection of paramagnetic contrast agent (Gadolinium-DTPA), for 54 DSM-IV patients with schizophrenia (mean age+/-SD=39.19+/-12.20 years; 34 males, 20 females) and 24 normal controls (mean age+/-SD=44.63+/-10.43 years; 9 males, 15 females) with a 1.5T Siemens magnet using an echo-planar sequence (TR=2160 ms, TE=47 ms, slice thickness=5mm). The contrast of enhancement (CE), a semi-quantitative parameter inversely estimating the CBV, were calculated pixel by pixel as the ratio of the maximum signal intensity drop during the passage of contrast agent (Sm) by the baseline pre-bolus signal intensity (So) (CE=Sm/Sox100) for right and left hemisphere on two axial images. Specifically, higher CE values correspond to lower CBV and viceversa Compared to normal controls, patients with schizophrenia had significantly higher bilateral hemisphere CE values (p=0.02) and inverse CE laterality index (p=0.02). This study showed abnormally reduced and inverse hemisphere CBV in a large population of patients with schizophrenia. Hypothetically, chronic low CBV may sustain neural hypoactivation and concomitant increase of free radicals, ultimately resulting in neuronal loss and cognitive impairments. Thus, altered intracranial hemodynamics may accompany brain atrophy and cognitive deficits, being a crucial factor in the pathophysiology of schizophrenia.

Normal pituitary volumes in chronic schizophrenia.

Pituitary volumes were shown to be abnormally large in pre- or first-psychotic episode patients and abnormally reduced in established schizophrenia by magnetic resonance imaging (MRI) studies. We present here the results of the second ever published MRI study exploring pituitary size in a large population of patients with chronic schizophrenia recruited from the geographically defined catchment area of South Verona, Italy. No significant differences for pituitary volumes were reported between 65 subjects with chronic schizophrenia and 65 normal individuals (mean age+/-S.D.=42.31+/-11.44 and 40.54+/-11.12 years). In contrast to Pariante et al. (2004), normal pituitary size was found in our population of chronic schizophrenia. Discrepancies between these two studies may partially be accounted by sample age and gender. Considering increased pituitary volumes in pre- or first-psychotic episode patients, we put forward the hypothesis that pituitary size may normalize or reduce with the progression of the illness as a result of reduced numbers of acute episodes and consequent diminished hypothalamus-pituitary-adrenal axis activity. To better test this hypothesis, future large MRI studies should investigate pituitary volumes in chronic schizophrenia longitudinally, also collecting pituitary hormones and cortisol, and comparing the effects of typical and atypical antipsychotics on pituitary size in a randomized trial.

Investigation of corpus callosum in schizophrenia with diffusion imaging.

BACKGROUND: Corpus callosum (CC) is the main white matter commissure between the two cerebral hemispheres. Abnormalities of CC have been shown in schizophrenia patients by magnetic resonance imaging (MRI) studies. We here further investigated CC organization with diffusion imaging (DWI) in a sample of schizophrenia patients recruited from the epidemiologically defined catchment area of South Verona, Italy. METHODS: Sixty-seven patients with schizophrenia and 70 normal controls were studied. Regions of interests (ROIs), standardized at 5 pixels, were placed in CC on the non-diffusion weighted echoplanar images (b = 0) and were then automatically transferred to the corresponding maps to obtain the apparent diffusion coefficient (ADC) of water molecules. RESULTS: ADC measures for all callosal subregions in schizophrenia patients were significantly greater compared to normal controls (ANCOVA, p < 0.05). Positive symptoms significantly correlated with anterior callosal ADC measures (partial correlation analyses, p < 0.05). CONCLUSIONS: These findings support the existence of widespread microstructure disruption of CC in schizophrenia, which may ultimately lead to inter-hemispheric misconnection, and also suggest a specific role of anterior transcallosal disconnectivity in underlying positive symptoms. Future longitudinal MRI studies in high risk and first-episode patients together with neurophysiological tests are indicated to further examine CC anatomical abnormalities and inter-hemispheric transmission in schizophrenia.

Acute Necrotizing Pancreatitis Following Olanzapine Treatment and 759C/T Polymorphism of HTR2C Gene: A Case Report.

Acute pancreatitis can be attributed to numerous potential causes, such as alcohol abuse, chololithiasis, infection, lesions, tumors, hypercalcemia, hyperlipidemia, and medications. Among psychotropic medications, the use of some atypical antipsychotics, such as clozapine, olanzapine, quetiapine and risperidone, has been implicated in the development of acute pancreatitis, although the underlying mechanism has not been clarified. We describe the case of a young man with no other major medical problems, alcohol abuse or predisposing factors, who developed acute necrotizing pancreatitis following olanzapine administration, possibly through severe elevation of serum triglycerides. A pharmacogenomic analysis revealed the presence of the 5-hydroxytryptamine (serotonin) receptor 2C, G protein-coupled (HTR2C) -759C genotype which is related to increased risk for metabolic syndrome.