Nielsen RE. Treatment of psychosis during pregnancy – a case report and a mini-review.

Objective: Describe clinical problems in treating a patient with psychotic symptoms during pregnancy by presenting a case report, and review the current evidence on antipsychotic drugs during pregnancy.

Methods: The review consists of a non-systematic clinical review of current data on treatment with antipsychotics during pregnancy. The case, a 27 year old female initially diagnosed with posttraumatic stress disorder (PTSD) after a rape and emotionally unstable personality disorder, illustrates some of the common challenges a clinician meets. The patient initially discontinues all treatment as she is unsure if the drugs could have a teratogenic effect and is changed to a treatment that is regarded as safe during pregnancy.

Results: The current data supports treatment with chlorpromazine although there is a risk of side effects, e.g. extrapyramidal symptoms and hypotension, but also treatment with olanzapine and risperidone. If the patient is currently treated with clozapine, this treatment should be continued, due to clozapines unique efficacy profile. Blood monitoring for six months after birth is recommended when the newborn has been exposed to clozapine treatment.

Conclusion: Current evidence on treatment with antipsychotics during pregnancy is sparse, but not treating is associated with increased risks compared to treatment.

Kim J-H, Ann J-H, Lee J. Relationship between heart rate variability and the severity of psychotic symptoms in schizophrenia.

Objective: The relationship between autonomic neurocardiac function and schizophrenia remains elusive. This study investigated the relationship between the heart rate variability (HRV) parameters and the severity of psychotic symptoms in schizophrenic patients.

Methods: Twenty-one patients receiving risperidone monotherapy and 21 matched normal control subjects were evaluated for HRV analysis. The severity of schizophrenic symptoms was assessed using the Positive and Negative Syndrome Scale (PANSS) and a five-factor model of the PANSS was used.

Results: The value of the ratio of low-to-high frequency spectral power was significantly higher in the patient group. The patient group also showed a significantly lower value of approximate entropy. After controlling the dosage of risperidone, the PANSS total score had significant negative correlations with the standard deviation of all RR intervals (SDNN) and the square root of the mean squared differences of successive normal sinus intervals (RMSSD). With respect to the PANSS factors, the score of the PANSS cognitive/disorganisation factor had significant negative correlations with SDNN and RMSSD.

Conclusion: These results provide some evidence that the severity of psychotic symptoms, especially cognitive/disorganisation symptom dimensions, may be associated with reduced HRV, suggesting a potential involvement of neuroautonomic dysfunction in the pathophysiology of specific symptoms of schizophrenia.

Agostinho FR, Réus GZ, Stringari RB, Ribeiro KF, Ferreira GK, Jeremias IC, Scaini G, Rezin GT, Streck EL, Quevedo J. Olanzapine plus fluoxetine treatment alters mitochondrial respiratory chain activity in the rat brain.

Background: Evidence is emerging for the role of dysfunctional mitochondria in pathophysiology and treatment of mood disorders. In this study, we evaluated the effects of acute and chronic administration of fluoxetine (FLX), olanzapine (OLZ) and the combination of FLX/OLZ on mitochondrial respiratory chain activity in the rat brain.

Methods: For acute treatment, Wistar rats received one single injection of OLZ (3 or 6 mg/kg) and/or FLX (12 or 25 mg/kg) and for chronic treatment, rats received daily injections of OLZ (3 or 6 mg/kg) and/or FLX (12 or 25 mg/kg) for 28 days and we evaluated the activity of mitochondrial respiratory chain complexes I, II, II–III and IV in prefrontal cortex, hippocampus and striatum.

Results: Our results showed that both acute and chronic treatments with FLX and OLZ alone or in combination altered respiratory chain complexes activity in the rat brain, but in combination we observed larger alterations.

Conclusions: Finally, these findings further support the hypothesis that metabolism energy could be involved in the treatment with antipsychotics and antidepressants in combination to mood disorders.

De Luca RD, Fraga DB, Ghedim FV, Kolling J, Ferreira AGK, Cunha AA, Wyse ATS, Zugno AI. Na+,K+-ATPase activity is increased in rats subjected to chronic administration of ketamine.

Objective: Schizophrenia is a devastating psychiatric disorder. Symptoms of schizophrenia can be divided into positive, negative and cognitive, and the physiopathology is still been unknown. Na+,K+-ATPase is a protein in its role as a maintainer of fluid balance in all mammals and alterations in this enzyme could cause brain abnormalities. The aim of our study was to investigate the activity of this enzyme in rats submitted to chronic administration of ketamine.

Methods: Adult male Wistar rats were submitted to sub-anaesthetic doses of the 25 mg/kg ketamine by seven consecutive days and the Na+,K+-ATPase activity was analysed in prefrontal and hippocampus of rats.

Results: We observed an increase in Na+,K+-ATPase activity in prefrontal cortex administration of 25 mg/kg ketamine. However, ketamine has no effect in hippocampus.

Conclusion: This evidence indicates that the alteration in Na+,K+-ATPase may be related with glutamatergic system and consequently could be related to the development of schizophrenia.

Kocer E, Kocer A, Degirmenci Y, Eryılmaz M. Long-term depression is a stroke risk factor.

Background and Aim: Only a few studies have evaluated depression prevalence in pre-stroke period in comparison to controls. We investigated this association based on a hospitalised stroke population.

Methods: One hundred and forty-eight stroke patients were evaluated. The presence of depression was compared with those of 100 healthy controls without stroke, from the same region. Depression was accepted as present or not present after history and clinical evaluation according to Diagnostic and Statistical Manual of Mental Disorders-IV. Socio-demographic variables, other stroke risk factors and the time of diagnosis of depression (how many year or month they got depression) were recorded.

Results: Gender and mean age of patients and controls were similar in comparison. Depression was diagnosed in 27 patients and 24 controls (p > 0.05). The time period passed after diagnosis of depression was longer in stroke patients in comparison to controls (p < 0.001).

Conclusions: The risk of stroke should be considered in elderly with long-term depression. This indicates that treatment of depression is another factor which should be considered in prevention of brain stroke.

Naismith SL, Rogers NL, Lewis SJG, Diamond K, Terpening Z, Norrie L, Hickie IB. Sleep disturbance in mild cognitive impairment: differential effects of current and remitted depression.

Objective: Although patients with mild cognitive impairment (MCI) commonly report sleep disturbance, the extent to which depressive symptoms contribute to this relationship is unclear. This study sought to delineate the contribution of current and remitted major depression (MD) to sleep disturbance in MCI.

Methods: Seventy-seven patients meeting criteria for MCI (mean age = 66.6 ± 8.8 years) were grouped according to those with no history of depression (MCI, n = 33), those meeting criteria for current MD [mild cognitive impairment and meeting criteria for current major depression (DEP-C), n = 14] and those with remitted MD [mild cognitive impairment and remitted major depression (DEP-R), n = 30]. Additionally, 17 healthy controls (CON) participated. Sleep was patient-rated using the Pittsburgh Sleep Quality Index and included assessment of sleep quality, duration, efficiency, disturbances, medications, sleep onset latency and daytime dysfunction. Depression severity was clinician-rated using the Hamilton Depression Rating Scale.

Results: Overall sleep disturbance was significantly greater in the DEP-C and DEP-R groups in comparison to the CON and MCI groups (p < 0.001). Only 12% of CON reported sleep disturbance, compared to 30% of MCI, 63% of DEP-R and 86% of DEP-C. Sub-scale analysis showed that the sleep disturbance in depressive groups was most evident across the domains of sleep quality, sleep efficiency, sleep latency and daytime dysfunction.

Conclusion: Sleep disturbance in MCI is strongly associated with a current or past diagnosis of MD. The finding that sleep complaints are still prominent in those with remitted depression, suggests that ‘trait' markers exist that may reflect underlying neurobiological changes within the sleep–wake system.

Williams LJ, Pasco JA, Jacka FN, Henry MJ, Dodd S, Nicholson GC, Kotowicz MA, Berk M. Bipolar disorder and adiposity: a study using whole body dual energy X-ray absorptiometry scans.

Objective: Previous research has demonstrated a relationship between adiposity and bipolar disorder, although data are derived predominantly from patient samples and use indirect methods of assessing adiposity. This study investigated the association between bipolar disorder and several indices of adiposity, including body fat mass as measured by dual energy X-ray absorptiometry (DXA), in a community-based sample.

Methods: In this study, 21 women with bipolar disorder and 523 healthy controls were drawn from an age-stratified, random, community-based sample of women (20–93 years) participating in the Geelong Osteoporosis Study. Bipolar disorder was diagnosed utilising a semi-structured clinical interview. Anthropometric measurements (weight, height, waist and hip circumference) were taken and fat mass was determined from whole body DXA scans (Lunar DPX-L).

Results Those with bipolar disorder tended to have greater adiposity. Age-adjusted mean (95% CI) values for bipolar versus controls according to adiposity indices were weight 75.6 (68.9–82.3) versus 72.6 (71.3–74.0) kg, waist circumference 89.8 (84.1–95.6) versus 87.3 (86.1–88.5) cm, waist:hip ratio 0.85 (0.82–0.87) versus 0.84 (0.83–0.84), body mass index 27.6 (25.1–30.1) versus 27.5 (27.0–28.0) kg/m2, fat mass 31.4 (26.5–36.3) versus 28.6 (27.5–29.5) kg and %body fat 40.4 (36.9–43.9) versus 38.0 (37.3–38.7)%; all p > 0.05. Further adjustment for height, smoking, alcohol, psychotropic medication, energy intake or physical activity did not influence these patterns.

Conclusion Although a pattern suggestive of greater adiposity among those with bipolar disorder was observed, no significant differences were detected. We cannot exclude the possibility of a type II error. Further research with a larger sample may produce more conclusive results.

Aydemir O, Akkaya C. Association of social anxiety with stigmatisation and low self-esteem in remitted bipolar patients.

Background: In remitted bipolar disorder, it is aimed to show the association between social anxiety, self-esteem and stigmatisation.

Methods: From two university clinics, a sample of 150 remitted bipolar patients was included in this study. Patients were assessed with Liebowitz Social Anxiety Scale, Rosenberg Self-Esteem Scale and sense of stigmatisation subscale of Bipolar Disorder Functioning Questionnaire (Stigma) and were rated with Hamilton Depression Rating Scale and Young Mania Rating Scale for mood symptoms. Confirmatory path analysis was performed.

Results: The mean age of the patients was 39.5, and 52.7% (n = 79) were female. Ninety per cent (n = 135) of the patients had bipolar I disorder. The mean duration of the illness was 13.4 years and the mean number of episodes was 7.8. The model was subjected to confirmatory path analysis and the goodness-of-fit index was calculated to be 0.909, the confirmatory fit index was found to be 0.902 and the root mean square error of approximation was 0.097. Self-esteem was negatively associated with stigmatisation (r = −0.746). Social anxiety was positively associated with self-esteem (r = 0.494). Social anxiety was negatively associated with stigmatisation (r = −0.381).

Conclusions: In remitted bipolar patients, social anxiety is very high and this social anxiety seems to be caused by self-stigmatisation and low self-esteem.

Dikmen M, Cantürk Z, Öztürk Y. Escitalopram oxalate, a selective serotonin reuptake inhibitor, exhibits cytotoxic and apoptotic effects in glioma C6 cells.

Objective: Various antidepressants, mainly tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs), have been reported to exhibit potent anticancer properties in different cancer cells. In this study, we evaluated the antiproliferative and apoptotic effects of escitalopram oxalate (25, 50, 100 and 200 µM) on rat C6 glioma cells.

Methods: Cell proliferations were measured by [3-(4,5-dimethylthiazol-2-yl)-2-5-diphenyltetrazolium bromide] (MTT) assay, apoptosis was observed by flow cytometric analysis on C6 cells.

Results: Significant decreases in the proliferation of C6 glioma cells were detected depending on increases in the escitalopram concentrations and incubation periods. When compared to controls, C6 cell proliferations after 24 h incubation were determined with 97.7, 85.9, 74.5 and 67.9% for 25, 50, 100 and 200 µM escitalopram, respectively, while the cell proliferations after 48 h were established as 96.5, 68.0, 50.7 and 39.9% for 25, 50, 100 and 200 µM concentrations, respectively. IC50 value of escitalopram was able to be calculated as 106.97 µM after 48 h. Based on Annexin V-propidium iodide (PI) binding capacity for 25, 50, 100 and 200 µM escitalopram, apoptotic effects were determined as 17.0, 22.3, 12.5 and 7.8%, respectively.

Conclusion: Based on our findings, escitalopram oxalate was observed to induce cytotoxic and apoptotic activities in C6 cells.

Earl J, Pop O, Jefferies K, Agrawal N. Impact of neuropsychiatry screening in neurological in-patients: comparison with routine clinical practice

Background: It is now well recognised that the rate of psychiatric comorbidity is high in patients with neurological disorders. Psychiatric comorbidity has a significant impact on quality of life and often goes undetected in routine clinical practice.

Objectives: To compare the rate of detection of psychiatric illness in routine clinical practice with the prevalence of mental illness established using a dedicated screening programme at a regional neuroscience centre and to assess if the screening programme had any enduring impact on routine clinical practice after its completion.

Methods: Consecutive admissions to a neurology ward in the 3-month period before (n = 160) and after (n = 158) a dedicated neuropsychiatric screening programme was carried out were identified. Case notes were then reviewed to establish if symptoms of mental illness were identified by the treating neurologists and if patients were referred for neuropsychiatric assessment. Rates of detection of neuropsychiatric problems and rates of referral for treatment were compared with those identified during the screening programme.

Results: In routine clinical practice, over two 3-month study periods, psychiatric symptoms were identified in 23.7% of patients and only 10.6% received neuropsychiatric interventions. This is much lower as compared with rates identified (51.3%) and treated (51.3%) during dedicated screening. Detection of mood symptoms decreased from 14.7% pre-screening to 3.8% in the post-screening period.

Conclusion: Rate of detection and treatment of neuropsychiatric problems remain low in neurology in-patients in routine clinical practice. Neuropsychiatric screening is effective but does not have sustained effect once it stops. Hence we suggest that active ongoing screening should be incorporated into routine practice.