The Associations of Neutrophil-Lymphocyte, Platelet-Lymphocyte, Monocyte-Lymphocyte Ratios and Immune-Inflammation Index with Negative Symptoms in Patients with Schizophrenia.

Neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR) and systemic immune-inflammation index (SII index) are increasingly used as indicators of inflammation in different conditions, including schizophrenia. However, their relationship with negative symptoms, including anhedonia, is largely unknown. Included were 200 patients with schizophrenia and 134 healthy controls (HC), assessed for physical anhedonia (PA), using the Revised Physical Anhedonia Scale (RPAS), and social anhedonia (SA) by the Revised Social Anhedonia Scale (RSAS). Patients were rated by the Positive and Negative Syndrome Scale (PANSS), the Clinical Assessment Interview for Negative Symptoms (CAINS) and the Brief Negative Symptom Scale (BNSS). Most of the negative symptoms were in a weak to moderate positive correlations with blood cell inflammatory ratios, namely, between NLR and MLR with PANSS negative scale, CAINS, and BNSS, and in male patients, between PLR and PANSS negative scale and CAINS. Fewer correlations were detected in females, but also in a positive direction. An exception was SA, given the negative correlation between its severity and the SII index in females, and its presence and higher PLR in males. While different negative symptoms were associated with subclinical inflammation, the relationship between SA and lower inflammatory markers deserves further exploration.

The Presence of Minor Physical Anomalies of a Hand in Patients with Mental Disorders.

INTRODUCTION: Minor physical anomalies (MPA) are subtle morphological deviations with little to none clinical significance that are developed prenatally and therefore could be an indicator of structural changes in the brain developing at the same time. Aim of this study was to determine whether the MPA of the hand can distinguish psychotic patients from patients with non-psychotic diagnoses as well as from the healthy individuals. SUBJECTS AND METHODS: 100 consecutive patients from the University Hospital Center Zagreb, Department of psychiatry, were included in this case-control study along with 100 healthy control subjects. Investigators examined the dorsal and palmar side of the hand and were blind to the patient's diagnoses previous to the examination. Examined MPA included thenar crease, proximal transverse crease, proximal interphalangeal joint, eponychium of the middle digit, fingernail size and digital flexibility. RESULTS: Results showed significant differences in the quantity of MPA between the patients and the control group, as well as differences between patients with psychosis and the healthy subjects. CONCLUSIONS: Despite the fact that previous studies demonstrated characteristic distribution of specific MPA in schizophrenia, this study did not prove such results. Moreover, this study showed that all the MPA are equally common in both schizophrenia and other psychoses.

Preliminary Assessment of Pre-Electroconvulsive Therapy Evaluation Practices in European Countries: The Need for Guidelines.

OBJECTIVES: Pre-electroconvulsive therapy (ECT) evaluation is an essential part of ECT preparation, a standard treatment in the psychiatric field. However, no routine pre-ECT evaluation has been published so far. This preliminary study aimed to explore different practices in pre-ECT evaluation across European countries. METHODS: The data were collected as a snowball sample approach using an online survey from September 2019 to April 2020. The final analysis included data from 18 clinics placed in 16 European countries. RESULTS: Regulations on the pre-ECT evaluation were found in 9 countries. All clinics reported doing complete blood count, serum electrolytes, and renal function analysis as a part of regular laboratory testing, alongside with a cardiovascular assessment. Ten clinics reported using psychiatric scales. Six clinics reported doing a cognitive assessment, of which all had regulations on the pre-ECT evaluation. Not one evaluation had the same sets of procedures and diagnostics. CONCLUSIONS: The differences in assessment approaches mirror high variability of the pre-ECT evaluation practice across Europe. Cognitive assessment and objectification of psychiatric symptoms should be a regular part of the pre-ECT evaluation because of the monitoring of the most common adverse effect and observing the clinical response to ECT. Standardization of the pre-ECT evaluation and ECT in general would remove criticisms and opposition to the treatment, make it based on the best of our knowledge, and provide a method respectful of patients' best interests and rights.

Phantom Earthquake Syndrome - A Pilot Study after Zagreb and Banovina 2020 Earthquake.

Impact of earthquake on mental health is well-documented globally. A number of earthquake survivors after Zagreb and Banovina earthquake in the year 2020 reported a phenomenon of phantom earthquake. Telephone pilot study on phantom earthquake symptoms was conducted with semi-structured interview in earthquake survivors. Phantom earthquake is manifested as a false sense of earthquake-motion, accompanied with vegetative and motor symptoms with psychological distress and behavioral change that interfere with expected daily functioning. We propose an operational model for the phantom earthquake syndrome and discuss possible underlying neurobiological mechanisms to be further investigated in studying of the phantom earthquake syndrome.

Add-on Oxytocin in the Treatment of Postpartum Acute Schizophrenia: A Case Report.

An increasing body of research has been published concerning the potential impact of oxytocin (OT) in the pathophysiology of neuropsychiatric disorders that affect social functioning, such as schizophrenia. The possible therapeutic effect of OT in promoting mother-child bonding could be valuable in the management of postpartum psychosis. Studies on the efficacy of OT as an add-on therapy in the treatment of schizophrenia have found reductions in both positive and negative symptoms. The patient in the case reported here developed her second psychotic episode at the age of 22, a month after delivering her first child. Four weeks after treatment with aripiprazole was initiated, the patient's negative symptoms persisted, causing problems in the mother-child interaction. Intranasal OT (40 IU/d) was then added to the aripiprazole. Assessment scales [the Positive and Negative Syndrome Scale (PANSS), the Disability Assessment Schedule (WHODAS 2.0), and the Barkin Index of Maternal Functioning (BIMF)] and qualitative data from her caregiver were obtained at baseline and in the third and eighth weeks after the end of the OT therapy. Improvement was observed on almost all of the domains of the WHODAS 2.0 and the BIMF, as well as on the PANSS negative and general psychopathology scales. Data from the patient's caregiver indicated an overall improvement in mother-child interaction. These results, especially the improvement in results on the PANSS scale, are similar to findings from previous studies in patients with schizophrenia. OT seems to boost the antipsychotic effect on positive symptoms through the OT dopamine pathway, while the effect on negative symptoms probably involves a more general mechanism. Because the postpartum period is of immense significance for child development and mental well-being, future research to investigate the therapeutic efficacy of OT in the management of postpartum psychosis is warranted.

Choline elevation in amygdala region at recovery indicates longer survival without depressive episode: a magnetic resonance spectroscopy study.

RATIONALE: Depression, with variable longitudinal patterns, recurs in one third of patients. We lack useful predictors of its course/outcome, and proton magnetic resonance spectroscopy (1H-MRS) of brain metabolites is an underused research modality in finding outcome correlates. OBJECTIVES: To determine if brain metabolite levels/changes in the amygdala region observed early in the recovery phase indicate depression recurrence risk in patients receiving maintenance therapy. METHODS: Forty-eight patients on stable-dose antidepressant (AD) maintenance therapy were analyzed from recovery onset until (i) recurrence of depression or (ii) start of AD discontinuation. Two 1H-MRS scans (6 months apart) were performed with a focus on amygdala at the beginning of recovery. N-acetylaspartate (NAA), choline-containing metabolites (Cho), and Glx (glutamine/glutamate and GABA) were evaluated with regard to time without recurrence, and risks were assessed by Cox proportional hazard modeling. RESULTS: Twenty patients had depression recurrence, and 23 patients reached AD discontinuation. General linear model repeated measures analysis displayed three-way interaction of measurement time, metabolite level, and recurrence on maintenance therapy, in a multivariate test, Wilks' lambda = 0.857, F(2,40) = 3.348, p = 0.045. Cho levels at the beginning of recovery and subsequent changes convey the highest risk for earlier recurrence. Patients experiencing higher amygdala Cho after recovery are at a significantly lower risk for depression recurrence (hazard ratio = 0.32; 95% confidence interval 0.13-0.77). CONCLUSION: Cho levels/changes in the amygdala early in the recovery phase correlate with clinical outcome. In the absence of major NAA fluctuations, changes in Cho and Glx may suggest a shift towards reduction in (previously increased) glutamatergic neurotransmission. Investigation of a larger sample with greater sampling frequency is needed to confirm the possible predictive role of metabolite changes in the amygdala region early in the recovery phase.

Attitudes Towards Older People in Croatian and Slovenian Nursing Students.

BACKGROUND: Croatia and Slovenia are neighboring countries with marked differences in high school and undergraduate nursing curricula. The aim was to assess and compare attitudes toward the elderly among undergraduate nursing students in Croatia and Slovenia and identify factors associated with positive/negative attitudes. SUBJECTS AND METHODS: This was a cross-sectional survey conducted between September, 2017 and July, 2018 among undergraduate nursing students at five higher education institutions: three in Slovenia and two in Croatia. The following data were gathered: age, sex, year of study, previous education, employment status, previous education in gerontolgy, desired professional role after graduating, previous experience with the elderly. Kogan`s Attitude Towards Old People Scale (KATOPS) score was the primary outcome measure. Pairwise comparisons were conducted between Croatian and Slovenian students. KATOPS score was dichotomized with values above the 3rd quartile considered excellent - the dichotomized score was used as the dependent variable in a binary logistic regression model. RESULTS: Overall, 825 students completed the questionnaire, 85.5% were women, 417 from Slovenia, 408 from Croatia, and 80% were under 22 years of age (80%). The average score on the KATOPS was 127.4, 95% CI 126.6-128.2. Variables associated with excellent scores on the KATOPS, based on the binary regression were: studying in Slovenia (OR=2.05, 95% CI 1.39-3.03), age group 28-32 years (OR=3.9, 95% CI 1.53-9.98); previous education gerontic nursing (OR=2.45, 95% CI 1.34-4.47), and full-time study (OR=2.12, 95% CI 1.38-3.55). Variables not associated with excellent scores were: being married (OR=0.44, 95% CI 0.22-0.92) and having previous experience in working with the elderly (OR=0.5, 95% CI 0.3-0.86). CONCLUSION: Attitudes toward old age are mildly positive in Slovenian and Croatian nursing students. Slovenian students have significantly more positive attitudes toward old age and these differences are most probably due to marked differences in undergraduate nursing curricula between the two countries.

Cognitive deficit in schizophrenia: an overview.

Depressive mood, anxiety, delusions, hallucinations and behavioral disturbances have been traditionally recognized as leading symptoms of mental disorders. However, cognitive symptoms went under-recognized or declined. Today there is robust evidence that cognitive dysfunction is present in the majority of mental disorders and is also related to impairments in the functioning of the persons with mental illness. It is proposed that aberrant brain neuronal network connectivity, arising from interplay of genetic, epigenetic, developmental and environmental factors, is responsible for cognitive decline. In schizophrenia, dysfunctions in working memory, attention, processing speed, visual and verbal learning with substantial deficit in reasoning, planning, abstract thinking and problem solving have been extensively documented. Social cognition - the ability to correctly process information and use it to generate appropriate response in situations, is also impaired. The correlation of cognitive impairment with functional outcome and employment, independent living and social functioning has emphasized the need for development of the treatments specific to cognition. It is considered that brain neuroplasticity allows for re-modulating and compensating the impairment process which could give opportunity to improve cognitive functions. Therefore, there is a need for comprehensive clinical assessment and follow-up of cognitive decline in mental illness. Implementation of specific treatment strategies addressing cognitive decline in mental illness, like new drugs, distinct cognitive-behavioural therapy, psychoeducation, social skills training and remediation strategies should be strongly indorsed targeting recovery and reduction of disability due to mental illness.

Choline and N-acetyl aspartate levels in the dorsolateral prefrontal cortex at the beginning of the recovery phase as markers of increased risk for depressive episode recurrence under different duration of maintenance therapy and after it: a retrospective cohort study.

AIM: To evaluate the relationship between the dynamics of proton magnetic resonance spectroscopy (1H-MRS) brain metabolite levels at the beginning of the recovery phase of the index depressive episode and the time to the recurrence of depression. METHODS: This retrospective cohort study analyzed the changes in N-acetyl aspartate (NAA), choline (Cho), and glutamate-glutamine in 48 patients with recurrent depression treated with maintenance antidepressant monotherapy at a stable dose. 1H-MRS was performed at the start of the recovery phase and 6 months later. 1H-MRS parameters, index episode descriptors, and depressive disorder course were analyzed by Cox proportional hazards model. RESULTS: NAA and Cho decrease six months after the beginning of the recovery period were time-independent risk factors for depressive episode recurrence. Hazard ratio associated with NAA decrease was 2.02 (95% confidence interval 1.06-3.84) and that associated with Cho decrease was 2.06 (95% confidence interval 1.02-4.17). These changes were not related to symptoms severity, as Montgomery-Asberg Depression Scale score remained generally unchanged (mean -0.01; standard deviation 1.6) over the first 6 months of recovery. CONCLUSION: Patients receiving maintenance antidepressant therapy after recovery who experience a decrease in NAA or Cho levels early in the recovery phase have a double risk of depressive episode recurrence. Sustained NAA and Cho levels at the beginning of the recovery phase may indicate increased brain resilience conferred by antidepressant therapy, while NAA and Cho decrease may indicate only the trait-related temporal effect of therapy in another stratum of patients.

Electroconvulsive therapy - general considerations and experience in Croatia.

Despite controversy, ECT has been recognized as significantly effective for the treatment of mental disorders since 1938, when Cerletti and Bini introduced ECT in clinical psychiatric practice for treatment of schizophrenia. In the next period, indication for ECT switched more toward depression and catatonia. ECT was even banned from psychiatric training in 1960's, due to the anti-psychiatric movement, which were fortified by Oscar winning movie "One Flew over the Cuckoo's Nest". Due to its robust effectiveness, ECT revived in the early 1980's and today holds its position in clinical psychiatric practices around the world. Mechanism of ECT on brain and psychopathology is still not fully understood. Main theories have been neurotransmitter, post-receptor, neurophysiological and neuroendocrine theory. Regarding best clinical practices and evidence reported in the literature, ECT today is considered a treatment option for, traditionally, depression, suicidality and catatonia, and also schizophrenia, schizoaffective disorder, bipolar disorder, malignant neuroleptic syndrome, postpartal depression and psychosis, obsessive compulsive disorder, post-traumatic stress disorder, dementia, etc. Recent evidence of ECT efficacy is growing stronger also in the treatment resistant cases, for depression and psychosis. Great advantage of ECT is lack of absolute contraindications. ECT in Croatia was introduced in clinical psychiatric practice in 1960's in four institutions. Mainly due to stigma, but also a tendency for shifting toward hypothesized action mechanism, ECT in Croatia has been re-named to electrostimulative therapy or electroneuromodulatory treatment. In recent decades, the Department of psychiatry in the University Hospital Centre Zagreb (KBC Zagreb), has continuously been practicing ECT. Our department is considered a regional leader, regarding number of patient cases and overall experience in homeland and neighbouring countries. In the 2016, Croatian expert group, selected by the Croatian Psychiatric Association, proposed national guidelines for the ECT. Research in ECT at our department has shown predominance of the treatment for therapy resistance in depression and psychosis. The other research at our department also showed improvement in several cognitive functions of patients after ECT application.

Brain-derived neurotrophic factor serum and plasma levels in the treatment of acute schizophrenia with olanzapine or risperidone: 6-week prospective study.

Antipsychotics have been the mainstay of the treatment of schizophrenia, and their potential role in neuroprotection could be related to brain-derived neurotrophic factor (BDNF). So far different effects on both serum and plasma levels of BDNF were reported related to the various antipsychotic treatments. Aim of this study was to investigate the influence of olanzapine or risperidone on both plasma and serum levels of BDNF in patients with acute schizophrenia. For 50 participants with acute episode of schizophrenia both plasma and serum BDNF, along with the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impression scale, were assessed pretreatment and post treatment - after 6 weeks of either risperidone or olanzapine. Results show that a weak correlation between pretreatment plasma and serum levels of BNDF was found no longer significant after 6 weeks of treatment. Antipsychotics, olanzapine and risperidone showed no significant effect on post treatment plasma and serum levels of BDNF. Pretreatment plasma level of BDNF and PANSS positive subscale were positively correlated. Post treatment serum level of BDNF and Clinical Global Impression were negatively correlated. In conclusion, plasma and serum BDNF levels could be different markers to some extent with regard to clinical symptoms, response to therapy and outcome. The interrelation between serum and plasma BDNF should be established in further studies.

Lower Choline-Containing Metabolites/Creatine (Cr) Rise and Failure to Sustain NAA/Cr Levels in the Dorsolateral Prefrontal Cortex Are Associated with Depressive Episode Recurrence under Maintenance Therapy: A Proton Magnetic Resonance Spectroscopy Retrospective Cohort Study.

BACKGROUND: The aim of this study was to evaluate the relationship between changes in proton magnetic resonance spectroscopy (1H-MRS) parameters at the start of the index episode recovery phase and at recurrence in patients with recurrent depression who were treated with prolonged maintenance therapy. METHODS: 1H-MRS parameters were analyzed in 48 patients with recurrent depression who required maintenance therapy with antidepressant medication prescribed by a psychiatrist and who continued with the same antidepressant during the maintenance phase, either to recurrence of depression, completion of the 10-year observation period, or the start of the withdrawal phase (tapering-off antidepressant). N-acetylaspartate (NAA), choline-containing metabolites (Cho), creatine (Cr), and glutamine/glutamate were measured at the start of the recovery phase and 6 months later. RESULTS: Recurrent depressive episodes occurred in 20 patients. These individuals had a smaller increase in Cho/Cr after the beginning of the recovery phase compared to the non-recurrent patient group and also exhibited a decreased NAA/Cr ratio. CONCLUSION: Sustainable NAA and increased Cho levels at the onset of the recovery phase of the index episode are early markers of antidepressant effectiveness associated with a lower risk of major depressive disorder recurrence. The NAA and Cho changes in the non-recurrent group may be attributable to increased brain resilience, contrary to the transient temporal effect observed in subjects who experienced a depressive episode.

No change in N-acetyl aspartate in first episode of moderate depression after antidepressant treatment: (1)H magnetic spectroscopy study of left amygdala and left dorsolateral prefrontal cortex.

BACKGROUND: The role of brain metabolites as biological correlates of the intensity, symptoms, and course of major depression has not been determined. It has also been inconclusive whether the change in brain metabolites, measured with proton magnetic spectroscopy, could be correlated with the treatment outcome. METHODS: Proton magnetic spectroscopy was performed in 29 participants with a first episode of moderate depression occurring in the left dorsolateral prefrontal cortex and left amygdala at baseline and after 8 weeks of antidepressant treatment with escitalopram. The Montgomery-Asberg Depression Rating Scale, the Hamilton Rating Scale for Depression, and the Beck Depression Inventory were used to assess the intensity of depression at baseline and at the endpoint of the study. At endpoint, the participants were identified as responders (n=17) or nonresponders (n=12) to the antidepressant therapy. RESULTS: There was no significant change in the N-acetyl aspartate/creatine ratio (NAA/Cr) after treatment with antidepressant medication. The baseline and endpoint NAA/Cr ratios were not significantly different between the responder and nonresponder groups. The correlation between NAA/Cr and changes in the scores of clinical scales were not significant in either group. CONCLUSION: This study could not confirm any significant changes in NAA after antidepressant treatment in the first episode of moderate depression, or in regard to therapy response in the left dorsolateral prefrontal cortex or left amygdala. Further research is necessary to conclude whether NAA alterations in the first episode of depression could possibly be different from chronic or late-onset depression, and whether NAA alterations in stress-induced (reactive) depression are different from endogenous depression. The potential role of NAA as a biomarker of a treatment effect has yet to be established.

The effect of atypical antipsychotics on brain N-acetylaspartate levels in antipsychotic-naïve first-episode patients with schizophrenia: a preliminary study.

PURPOSE: To investigate the correlates of a clinical therapeutic response by using the parameters measured by proton magnetic resonance spectroscopy after the administration of atypical antipsychotics. PATIENTS AND METHODS: Twenty-five antipsychotic-naïve first-episode patients with schizophrenia were monitored for 12 months. The patients were evaluated using (1)H magnetic resonance spectroscopy in the dorsolateral prefrontal cortex and Positive and Negative Syndrome Scale, Clinical Global Impression Scale of Severity, Tower of London - Drexel University, Letter-Number Span Test, Trail Making Test A, and Personal and Social Performance Scale. They were administered atypical antipsychotics, starting with quetiapine. In the absence of a therapeutic response, another antipsychotic was introduced. RESULTS: After 12 study months, the N-acetylaspartate/creatine (NAA/Cr) level did not significantly change at the whole-group level. Additional analysis revealed a significant rise in the NAA/Cr level in the study group that stayed on the same antipsychotic throughout the study course (P=0.008) and a significant drop in NAA/Cr in the study group that switched antipsychotics (P=0.005). On the whole-group level, no significant correlations between NAA/Cr values and other scores were found at either baseline or after 12 study months. CONCLUSION: One-year treatment with atypical antipsychotics administered to antipsychotic-naïve patients didn't result in a significant rise in the NAA/Cr ratio. However, a significant rise was witnessed in the study group in which a satisfactory therapeutic response had been achieved with a single antipsychotic administration.

Comparison of hippocampal volumes in schizophrenia, schizoaffective and bipolar disorder.

The reduction of hippocampal volume was frequently reported in schizophrenia, but not in bipolar disorder This volume reduction is associated with clinical features of schizophrenia, in particular with working and verbal memory impairments. Schizoaffective disorder, as a specific disorder sharing clinical features of both schizophrenia and bipolar disorder is rarely analyzed as a separate disorder in neurobiological studies. The aim of this study was to compare hippocampal volumes in separate groups of patients with schizophrenia, schizoaffective and bipolar disorder. Hippocampal volumes were estimated using high resolution magnetic resonance imaging in 60 subjects, 15 subjects in each patient and one healthy volunteer (control) group. There were no significant differences in hippocampal volume between bipolar disorder and control group. Hippocampal volume was statistically significantly reduced in the group of patients with schizophrenia and schizoaffective disorder, compared to either bipolar disorder or control group, thus supporting the hypothesis that hippocampal volume reduction could be considered as a possible neurobiological basis for clinical aspects of schizophrenia and schizoaffective disorder associated with working and verbal memory impairment.