Major Depression and Onset of Frontotemporal Dementia.

Purpose: Frontotemporal dementia (FTD) is still a clinical challenge with the highest rate of misdiagnosis and poor outcome. The pathogenetic relationship between depression and neurodegeneration remains unclear. This study evaluated depression prevalence before FTD diagnosis. Patients and Methods: The aim was to assess the prevalence and impact of depression on FTD diagnostic process. The clinical characteristics of 72 patients hospitalized in Department of Affective and Psychotic Disorders Medical University of Lodz between 2010 and 2020 with final diagnosis FTD were analyzed. The data referring to first psychiatric diagnosis, time from first psychopathological symptoms to clarification of FTD diagnosis were collected. The patients who did not undergo full neuropsychiatric verification were excluded from the analysis. Results: About 69% of patients had other concomitant diagnosis of mental disorders which was made prior to FTD diagnosis. Among this subsample, 71% revealed depression diagnosis with at least moderate severity. The patients whose first diagnosis was psychotic depression revealed the longest period from the appearance of the first psychopathological symptoms to the diagnosis of FTD in comparison to the subsample with other psychiatric diagnosis (p=0.034; mean 4.33±3.28 years vs mean 2.68±1.39 years). Conclusion: The severe depressive symptoms in older age may reflect the development of neurodegeneration before full-blown frontotemporal dementia symptomatology. We hypothesized that psychotic depression is a predictor of FTD. Further investigations in this field are required.

The Relationship Between Antipsychotic Treatment and Plasma ß-Endorphin Concentration in Patients with Schizophrenia.

OBJECTIVE: Some studies indicate the presence of elevated opioid levels in cases of schizophrenia and their relationship with negative symptoms. The pathogenesis of schizophrenia may be associated with an imbalance in the modulatory effect of opioids on the dopaminergic system. The aim of the study was to identify the association between ß-endorphin (BE) concentration and the outcome of short-term schizophrenia treatment. METHODS: We examined 49 patients hospitalized due to exacerbation of schizophrenia symptoms and 47 controls without schizophrenia. The severity of psychopathological symptoms was evaluated using Positive and Negative Syndrome Scale (PANSS) at the onset of hospitalization, and after four, six and ten weeks of treatment. Patients were classified into negative (NEG) and mixed (M) psychopathological subtypes according to the PANSS composite index. Β-endorphin (BE) plasma concentrations were assessed in all participants; in patients on inclusion to the study and after six weeks of treatment. RESULTS: The patients with schizophrenia demonstrated higher BE levels than controls. During six-week antipsychotic treatment, BE concentration significantly increased in both NEG (p=0.000) and M (p=0.007), and positive symptoms were effectively reduced. In the NEG group, the prevalence of negative symptoms decreased only transiently and returned to approximately baseline values after 10 weeks (p=0.268). In the M patients, the prevalence of negative symptoms increased gradually (p=0.001), with more severe positive and, notably, negative symptoms correlating with higher BE2 concentrations at the 10-week assessment (R= 0.47, p= 0.0135 vs R= 0.74, p=0.0000). In both NEG and M, a greater rise in BE2 level correlated with a lower composite index during treatment. CONCLUSION: Patients with schizophrenia demonstrate higher BE levels compared to controls. These changes in BE concentration during antipsychotic treatment could reflect the interaction between dopaminergic transmission and endogenous opioids. A rise in BE level following effective antipsychotic therapy could be a potential predictor of persisting negative symptoms.

Plasma ß-Endorphin Concentration and Antipsychotic Treatment Outcome in Schizophrenia: 1-Year Follow-Up.

BACKGROUND Increased levels of endogenous opioids have been observed in patients with schizophrenia; however, the influence of these endogenous opioids on the biology of schizophrenia remains unclear. The aim of this study was to evaluate the impact of beta-endorphin (BE) on the course of schizophrenia and risk of relapse. MATERIAL AND METHODS The study included 25 patients hospitalized with schizophrenia and 47 controls. Their symptoms were evaluated using Positive and Negative Syndrome Scale (PANSS) and composite index at five points: at the onset of hospitalization; after 4, 6 and 10 weeks of treatment; and after 12 months. ß-endorphin plasma concentrations were assessed in patients at study enrollment and after 6 weeks of treatment. Data regarding rehospitalization during follow-up were also collected. RESULTS Patients had higher BE concentration than controls at study enrollment (P=0.002) and after 6 weeks (P=0.000). BE levels increased during treatment (mean 0.538ng/mL vs. mean 0.624 ng/mL; P=0.007). No correlation was found between BE concentration and PANSS subscale score at any stage of the study. A higher BE level at study enrollment was related to a predominance of negative symptoms after 1 year, measured with composite index (R=-0.404; P=0.045). Patients who were later hospitalized again were significantly more likely to demonstrate an increase in BE levels over 6 weeks (P=0.001). CONCLUSIONS Individuals with schizophrenia demonstrated higher BE concentrations than healthy controls; this tendency was particularly apparent in those affected by negative symptoms. The imbalance in the endogenous opioid system might adversely alter the course of disease and predispose patients to persistence of negative symptoms, despite antipsychotic treatment.

A developmentally-stable pattern of premorbid schizoid-schizotypal features predicts psychotic transition from the clinical high-risk for psychosis state.

BACKGROUND: Despite the extensive research performed on prediction of psychosis from a Clinical High Risk for Psychosis state (CHR-P), the positive predictive value of the CHR-P designation remains unsatisfactory and further models including additional clinical and biological variables are required. Existing studies indicate that schizotypy assessed at baseline in "at-risk" individuals may be considered a predictor of transition from CHR-P to psychosis. This approach, however, is burdened with bias resulting from a possible overlap between current psychopathology and schizotypal features. No studies so far have assessed schizotypy in CHR-P from a developmental perspective. AIM: The aim of the study was to identify associations between a long-standing, parent-reported premorbid level of schizoid-schizotypal traits and the probability of psychotic transition in individuals with CHR-P. METHODS: The mothers of 107 individuals diagnosed as presenting CHR-P with the use of Comprehensive Assessment of At Risk Mental States12/2006 were interviewed with the Scale for the Assessment of Premorbid Schizoid-Schizotypal Traits (PSST). RESULTS: A high level of enduring schizotypy was found to be significantly associated with psychotic transition from CHR-P (HR: 1.78, 95% CI: 1.40-2.27, p < 0.0001), as indicated by the proportional hazards model, adjusted for age, sex and clinical covariates potentially related to the outcome. PSST items comprising negative schizotypy appeared to be the strongest predictors of transition. CONCLUSIONS: The assessment of parent-reported, present early in the development premorbid schizoid-schizotypal traits, which can be easily performed in clinical settings, may be of value in estimating the probability of transition from an "at risk" state to psychotic disorder.

Odor perception and hedonics in chronic schizophrenia and in first episode psychosis.

BACKGROUND AND PURPOSE: The study evaluated olfactory performance and pleasantness rating of odors in patients with first episode psychosis (FEP) and chronic schizophrenia (SCH) with regard to the severity of psychopathological symptoms and plasma ß-endorphin concentration. PATIENTS AND METHODS: Twenty patients with FEP, 27 with SCH and 29 healthy individuals, were recruited to the research . The University of Pennsylvania Smell Identification Test (UPSIT), subjective odor hedonic judgment and plasma levels of ß-endorphin (BE) assay were performed in all participants. RESULTS: Individuals with SCH revealed higher BE concentration than other study groups (P=0.000). All patients identified pleasant odors poorer than controls, however, SCH made more identification errors (P=0.000) than those with FEP. Moreover, participants with FEP rated pleasant odors as more pleasant than individuals with chronic schizophrenia and healthy controls (P=0.009). Nevertheless, higher ß-endorphin level was related with lower scores in pleasant odor identification (Rs=-0.452; P=0.046) and more severe psychotic symptoms in FEP sample. Chronic schizophrenia patients did not demonstrate any relationship between symptom severity, odor identification performance and ß-endorphin concentration. No relationship was found between BE concentration and hedonic judgment of the presented odors among all study groups. Chronically ill subjects identified odors significantly more poorly than those with first episode psychosis. Deficits in identifying pleasant odors might not be the only potential risk factor for undergoing chronic, recurrent schizophrenia. All patients subjectively overrated pleasant odors. Those with SCH and more severe negative symptoms made significantly more identification errors. CONCLUSION: The endogenous morphine system deregulation is observed in first episode psychosis as well as in chronic schizophrenia. In first episode schizophrenia higher beta-endorphin concentration is related to pleasant odor identification deficit.

The Relationship Between Course of Illness and ß-Endorphin Plasma Levels in Patients with Schizophrenia.

OBJECTIVE: Extensive investigations have been conducted into predictors of schizophrenia outcome. The heterogeneity of the illness implies that many factors should be taken into account. Some studies have reported the relationship between increased ß-endorphin concentration and predominant negative symptoms. METHODS: We included 77 outpatients with schizophrenia and 74 healthy controls. Data referring to duration and course of illness, hospitalization number and treatment were collected on the basis of clinical interviews and medical documentation analysis. The ß-endorphin concentrations were assessed once in all participants, at the onset of the study. RESULTS: A chronic course of illness was found in 44 of the 77 schizophrenics. Patients with schizophrenia, especially those with a chronic course of illness, revealed significantly higher ß-endorphin concentrations than those with an episodic course and controls (mean 29.70 vs 19.86 pmol/L; p=0.0001). Increased levels of ß-endorphin were related to longer duration of illness (R=0.294, p=0.009) and frequent psychiatric hospitalization (R=0.346, p=-0.002). CONCLUSION: Endorphins may be potential biological predictors of persistent negative symptoms and final outcome in schizophrenia.

Serum levels of TNF-alpha in patients with chronic schizophrenia during treatment augmentation with sarcosine (results of the PULSAR study).

Sarcosine, glycine transporter inhibitor, increases glycine levels around NMDA receptor, improving primary negative symptoms of schizophrenia. The aim of our study was to find a potential relationship between initial TNF-alpha level, its changes and schizophrenia symptoms severity, resulting from adding sarcosine to a stable antipsychotic treatment. Sixty subjects with stable schizophrenia were randomized to receive either 2 g of sarcosine or placebo and completed a 6-month, double blind, placebo-controlled study. Three patients on sarcosine and one taking placebo did not complete TNF-alpha tests, planned at the beginning, after 6 weeks and after 6 months. For clinical assessments we used PANSS and CDSS scales. No changes in TNF-alpha serum concentrations in both groups at any time-points was noted. The sarcosine group achieved significant improvement in negative symptoms, general psychopathology and total PANSS score group, however without any significant correlations between TNF-alpha levels and PANSS scores in all assessments. Positive correlations between TNF-alpha levels and CDSS score were found in the placebo group and total study group. Initial TNF-alpha concentrations cannot be used as a predictor of the improvement resulting from adding sarcosine. Sarcosine does not significantly affect TNF-alpha levels. TNF-alpha may be involved in mechanisms related to depressive symptomatology in schizophrenia.

Overrated hedonic judgment of odors in patients with schizophrenia.

AIMS: The odor identification ability and its hedonic judgment in patients with schizophrenia were evaluated in the study. The association between olfactory performance and negative symptoms and ß-endorphin concentration was also analyzed. METHODS: Study groups consisted of 23 patients with negative symptoms (PN) and 25 without predominant negative symptoms (PP) and 21 healthy individuals. The University of Pennsylvania Smell Identification Test, odor hedonic evaluation, and plasma concentrations of ß-endorphin assay in all participants were performed. RESULTS: PN perceived the poorer olfactory identification; nevertheless, they evaluated unpleasant odors as more pleasant than PP and controls. Beta-endorphin concentration was significantly higher among PN than in other study groups. No association was observed between ß-endorphin and odors identification and odor hedonic judgment among all study groups. CONCLUSIONS: There is potential relationship between increased ß-endorphin concentration and severity of negative symptoms. Patients with predominant negative symptoms tend to evaluate odors as significantly more pleasant. Individuals with this subtype of schizophrenia might present specific, altered pattern of smell identification and hedonic judgment. Presumably, ß-endorphin has no direct influence on olfactory identification performance and hedonic judgment in schizophrenia.

Serum levels of interleukin 6 in schizophrenic patients during treatment augmentation with sarcosine (results of the PULSAR study).

OBJECTIVE: Augmentation of sarcosine, a natural inhibitor of the glycine transporter type I, normalizes glutamatergic neurotransmission, having beneficial impact on primary negative symptoms in schizophrenia and may also influence immune system and interleukin 6 (IL-6) levels. AIM: Finding a relationship between initial IL-6 serum concentrations or its changes and severity of symptoms as a result of sarcosine addition to stable antipsychotic treatment. METHOD: Fifity-eight individuals with schizophrenia with predominantly negative symptoms completed a 6-month randomized, double-blind placebo-controlled prospective study. Patients received 2 g of sarcosine (n = 29) or placebo (n = 30) daily per os. We measured IL-6 levels and severity of symptoms at the beginning, after 6 weeks and 6 months. As main clinical tools, we used Positive and Negative Syndrome Scale (PANSS) and Calgary depression scale for schizophrenia (CDSS). RESULTS: Augmentation with sarcosine had no effect on IL-6 serum levels in all time points. We noted significant improvements in negative symptoms, general psychopathology, and total PANSS score in the sarcosine group. We found correlation of initial serum IL-6 with severity of positive symptoms and negative association between IL-6 levels reduction and positive symptoms reduction. CONCLUSIONS: Sarcosine does not significantly affect IL-6 concentrations but IL-6 may be involved in mechanisms related to the presence of positive symptoms.

Deficits in the identification of pleasant odors predict the transition of an at-risk mental state to psychosis.

OBJECTIVE: Existing knowledge of the relationship between olfactory identification (OI) ability and clinical risk of psychosis is inconsistent. To address this inconsistency, the aim of the present study was to identify the relationship between OI ability, with regard to the hedonic attributes of odors, and the risk of transition to psychosis in individuals with an ARMS. METHODS: A group of 81 individuals meeting the ARMS criteria according to the Comprehensive Assessment of At Risk Mental State were at baseline administered with the University of Pennsylvania Smell Identification Test. The hedonic attributes of odorants were normatively established. Participants were followed up for transition to psychosis for a mean period of 36.1months (SD:27.5months). RESULTS: The presence of deficits in the identification of pleasant odors was found to be a risk factor for conversion from an ARMS to schizophrenia. The hazard ratio for each point in deficit scores in the Cox regression model was 1.455 (95% CI: 1.211-1.747), p<0.0001. Significant deficits in the identification of pleasant odors were associated with a risk for conversion at both early and late time points from baseline. CONCLUSIONS: The findings imply that the impaired identification of pleasant odorants may be a risk factor for the transition of an ARMS into a psychotic disorder, and highlights the need for further research of OI in "at-risk" cohorts, taking into account the hedonic attributes of odors.

Comparison of beta-endorphin and CGRP levels before and after treatment for severe schizophrenia.

OBJECTIVES: Links between endorphins and dopaminergic transmission have not been fully explored in schizophrenia. Both endorphins excess and deficiency were postulated. CGRP is probably involved in dopaminergic transmission. The aim of this study was the evaluation of beta-endorphin (BE) and CGRP blood concentrations before and after treatment of severe schizophrenia. METHODS: Seventy patients treated with various antipsychotics, with severe symptoms of schizophrenia (51 with positive symptoms, 19 with negative symptoms), 15 first-degree relatives, and 44 healthy controls were included in the study. BE and CGRP blood concentrations were measured during patients severe schizophrenia and in their stable mental state after treatment. The results were compared with relatives and controls. RESULTS: BE and CGRP concentrations in patients with negative symptoms were higher than in relatives and in controls. BE levels in patients with positive symptoms were lower than in patients with negative symptoms (P<0.0000) and controls (P<0.0006). No significant changes in CGRP concentration were found in patient samples. CGRP levels in these samples were independent of treatment, but they were significantly higher than in relatives and controls. After the treatment, BE level decreased in patients with negative symptoms (P<0.0001) and increased in patients with positive symptoms (P<0.0000). No differences in BE concentration between patients in stable mental state, their relatives, and controls were found. CONCLUSION: Effective antipsychotic treatment results in "normalization" of BE level. Specific changes in BE concentration could be involved in dopaminergic transmission and related to some symptoms of schizophrenia.

Pain perception in schizophrenia: influence of neuropeptides, cognitive disorders, and negative symptoms.

OBJECTIVES: The causes and nature of insensitivity to pain in schizophrenia remain unknown. The role of endorphins and the association of cognitive dysfunction and negative symptoms are postulated. METHODS: In this study, 43 patients with schizophrenia, five first-degree relatives, and 34 healthy controls were examined. Participants' plasma concentrations of substance P, ß-endorphin, and calcitonin gene-related peptide (CGRP) were assessed. In patients, the Trail-Making Test, the Color Reading Interference Test (Stroop test), and the Positive and Negative Syndrome Scale Negative Syndrome subscale (PANSS N) test were performed. We also evaluated pain threshold using nociceptive reflex (RTIII) testing. RESULTS: The mean ß-endorphin concentration was about 20% higher in patients than in healthy controls (P<0.05). CGRP concentrations were significantly higher in patients than in controls (5.34 ng/mL versus 4.16 ng/mL; P<0.01). Subjects treated with antipsychotic polytherapy had higher concentrations of CGRP than did patients treated with second-generation antipsychotic monotherapy (5.92 ng/mL versus 5.02 ng/mL; P<0.05). There were no correlations between any biochemical parameters and Trail-Making Test, Stroop test, and PANSS N scores. There were no differences in RTIII among study groups. Strong negative correlation (P<0.001) was found between PANSS N scores and subjective pain threshold on the right lower limb. CONCLUSION: The insensitivity to pain in schizophrenia is a complex phenomenon that is probably not related to changes in nociceptive pathways. Increase in ß-endorphin level may be related to this issue, but it is uncertain if such concentration ensures analgesic effect. It is unknown if patients with schizophrenia in fact experience less pain. Cognitive impairment and excess negative symptoms may strongly influence the patient's expression of pain.

Neuropsychiatric symptoms and celiac disease.

BACKGROUND: Neuropsychiatric symptoms may represent an atypical manifestation of celiac disease that occur before a gastroenterological diagnosis is made. Some studies suggest that a gluten-free diet is effective in treating the depression, anxiety, and neurological complications associated with celiac disease. METHOD: The article describes the case of a patient suffering from chronic, treatment-resistant symptoms of depression and anxiety. The diagnosis of celiac disease and introduction of an elimination diet caused a significant improvement in mental state and everyday functioning in the presenting patient. CONCLUSION: The presence of persistent anxiety and depressive symptoms, with a poor reaction to pharmacological treatment, indicates a need to identify somatic reasons for the underlying condition. It is important to remember that celiac disease can occur at any age, not only in childhood. The presence of this somatic cause of persistent depressive and anxiety symptoms should be considered in the diagnostic process in adults.

Electroconvulsive therapy in patient with psychotic depression and multiple sclerosis.

Safety of electroconvulsive therapy (ECT) in depressive patients with multiple sclerosis (MS) is still discussed and based solely on case reports. This kind of therapy was used in both unipolar depression and depression in bipolar disorder. It was suggested that ECT might cause the deterioration of neurological state (new MS lesions in magnetic resonance imaging). Moreover, there were also data indicating some anesthesiological complications and difficulties in patients with MS. We have presented a case of a patient who was treated with ECT and developed grand mal seizure after 14th electroconvulsive treatment.