Lipid effects during antipsychotic drug treatment and their relevance for clinical outcomes

Schizophrenia is a devastating mental disorder with disease mechanisms that are still poorly understood. Evidence has emerged that lipid dysregulations and myelination abnormalities might contribute to the pathophysiology of schizophrenia. Antipsychotic drugs often induce severe metabolic adverse effects, such as weight gain, dyslipidemias, and diabetes. However, several studies in chronic patients have indicated that some antipsychotic drug-related metabolic changes may be associated with improvements in psychotic symptoms. The main aim of this doctoral thesis was to combine clinical, biological, and imaging data to increase our current understanding of the relationship between serum lipid changes and various outcomes in antipsychotic-treated patients earlier in their illness course with emphasis on first-episode psychosis (FEP) patients. The clinical samples included FEP patients using antipsychotic drug treatment, olanzapine-treated, and unmedicated patients with broad schizophrenia spectrum disorders, along with a group of healthy controls from the Thematically Organized Psychosis project in Oslo. The participants underwent a thorough clinical evaluation, structural imaging, analyses of serum lipids, and physical examination, including assessment of body mass index (BMI). The severity of positive and negative symptoms and cognitive performances were assessed at inclusion and after a one-year follow-up, along with serum lipids. Linear mixed-effects models were used to examine associations between changes in serum lipids versus changes in positive, negative, and cognitive symptoms. General linear models were used to investigate associations between serum lipids and cortical thickness and gray/white matter intensity contrast, which were used as proxy measures for intracortical myelin. Our results indicate that an increase in serum HDL-C during antipsychotic drug treatment is associated with improvements in negative symptoms and verbal learning, independent of changes in BMI. Moreover, OLZ treatment was linked to normalized cortical intensity contrast, and a higher serum level of HDL-C in OLZ-treated patients was related to thicker cortices suggesting a lipid-mediated effect on intracortical myelin. Together, our results may indicate that the therapeutic effect of antipsychotic drug treatment could in parts be linked to lipid biosynthesis

Sex-Specific Effect of Serum Lipids and Body Mass Index on Psychotic Symptoms, a Cross-Sectional Study of First-Episode Psychosis Patients

Background: Schizophrenia is a disorder with considerable heterogeneity in course and outcomes, which is in part related to the patients' sex. Studies report a link between serum lipids, body mass index (BMI), and therapeutic response. However, the role of sex in these relationships is poorly understood. In a cross-sectional sample of first-episode psychosis (FEP) patients, we investigated if the relationship between serum lipid levels (total cholesterol, HDL-C, LDL-C, and triglycerides), BMI, and symptoms differs between the sexes. Methods: We included 435 FEP patients (males: N = 283, 65%) from the ongoing Thematically Organized Psychosis (TOP) study. Data on clinical status, antipsychotics, lifestyle, serum lipid levels, and BMI were obtained. The Positive and Negative Syndrome Scale (PANSS) and the Calgary Depression Scale for Schizophrenia (CDSS) were used to assess psychotic and depressive symptoms. General linear models were employed to examine the relationship between metabolic variables and symptomatology. Results: We observed a female-specific association between serum HDL-C levels and negative symptoms (B = −2.24, p = 0.03) and between triglycerides levels (B = 1.48, p = 0.04) and BMI (B = 0.27, p = 0.001) with depressive symptoms. When controlling for BMI, only the association between serum HDL-C levels and negative symptoms remained significant. Moreover, the HDL-C and BMI associations remained significant after controlling for demography, lifestyle, and illness-related factors. Conclusion: We found a relationship between metabolic factors and psychiatric symptoms in FEP patients that was sex-dependent.publishedVersio

Lifetime Cannabis Use Is Not Associated With Negative Beliefs About Medication in Patients With First Treatment Psychosis

Objective: Cannabis use is common among patients with psychosis, and along with negative beliefs about medication, it has been found to predict poor adherence to antipsychotic drug treatment. Such lack of adherence to antipsychotic drug treatment increases the risk of poor clinical outcomes and relapse in patients with first treatment for psychosis (FTP). However, to date, it is unclear whether cannabis use may be related to negative perceptions about antipsychotic drug treatment. Methods: A cross-sectional sample of 265 FTP patients with schizophrenia spectrum disorder underwent extensive clinical assessments. Three measures of cannabis use were obtained: lifetime, current and meeting diagnostic criteria for abuse or addiction. For the primary analyses we focused on lifetime cannabis use. The Beliefs about Medication Questionnaire (BMQ) was employed to assess the patients' specific concerns and perceptions of antipsychotic medications, as well as general beliefs about pharmacotherapy. The relationship between lifetime cannabis use and BMQ scores was investigated with general linear model (GLM) analyses, controlling for age and sex. Results: Patients with lifetime use of cannabis ≥10 times were more likely to be male, younger at the age of onset of psychosis and with higher levels of alcohol use and daily tobacco smoking, as compared to the non-users (p < 0.05). Neither lifetime use of cannabis, current use nor a cannabis abuse diagnosis was associated with negative beliefs about medicines as measured by the BMQ questionnaire. Conclusion: Use of cannabis is not linked to negative perceptions about antipsychotic medicines in patients with FTP. Other reasons for poor compliance to antipsychotic drug treatment in cannabis users need to be further investigated.publishedVersio

Improvement in verbal learning over the first year of antipsychotic treatment is associated with serum HDL levels in a cohort of first episode psychosis patients

To investigate whether changes in serum lipids are associated with cognitive performance in first episode psychosis (FEP) patients during their first year of antipsychotic drug treatment. One hundred and thirty-two antipsychotic-treated FEP patients were included through the TOP study along with 83 age- and gender-matched healthy controls (HC). Information regarding cognitive performance, psychotic symptoms, lifestyle, body mass index, serum lipids [total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein cholesterol, and triglycerides] and antipsychotic treatment was obtained at baseline and after 1 year. The cognitive test battery is comprised of assessments for verbal learning, processing speed, working memory, verbal fluency, and inhibition. Mixed-effects models were used to study the relationship between changes over time in serum lipids and cognitive domains, controlling for potential confounders. There was a significant group by HDL interaction effect for verbal learning (F = 11.12, p = 0.001), where an increase in HDL levels was associated with improvement in verbal learning in FEP patients but not in HC. Practice effects, lifestyle, and psychotic symptoms did not significantly affect this relationship. Antipsychotic-treated FEP patients who increased in HDL levels during the first year of follow-up exhibited better verbal learning capacity. Further investigations are needed to clarify the underlying mechanisms.publishedVersio

Livmorhalsprøvetaking i primærhelsetjenesten

BAKGRUNN I Norge ble det i 2020 tatt ca. 360 000 screeningprøver fra livmorhals, hvorav 11 000 ble registrert som uegnede. Vi ønsket derfor å undersøke kunnskap om livmorhalsprøvetaking blant leger i primærhelsetjenesten. MATERIALE OG METODE En anonym spørreundersøkelse om livmorhalsprøvetaking ble sendt på e-post til de ca. 4 700 medlemmene i Norsk forening for allmennmedisin i september 2021. RESULTATER Av de 1 039 legene som svarte på undersøkelsen, oppga 820 (79 %) at de alltid fyller ut årsak til prøvetaking i rekvisisjonen, og 898 (86 %) opplyste at de unngår å ta prøve ved menstruasjon. Bare én av tre leger (343) anga riktig lokalisering av overgangssonen hos postmenopausale kvinner. På spørsmål rettet til brukere av metoden som er spesielt følsom for prøvetakingsfeil (ThinPrep), svarte 426 av 697 (61 %) at de enten unngår eksplorasjonskrem eller bruker vannbasert krem, mens kun 35 % av legene svarte at de stopper prøvetakingen hvis blødning oppstår. FORTOLKNING Resultatene viser at selv om kunnskapen hos mange er god, er kontinuerlig fokus på livmorhalsprøvetaking viktig. Riktig prøvetaking samt kjennskap til anatomiske forhold hos postmenopausale kvinner kan være av betydning for å redusere antallet uegnede prøver. Hovedfunn Leger i primærhelsetjenesten viste generelt god kunnskap om prøvetaking fra livmorhals, men 65 % kunne ikke angi korrekt hvor celleprøve skal tas hos postmenopausale kvinner. Blant legene som benyttet ThinPrep, stoppet 35 % prøvetaking hvis blødning oppsto, og 61 % svarte korrekt på spørsmål om bruk av eksplorasjonskrem.publishedVersio

Lipid effects during antipsychotic drug treatment and their relevance for clinical outcomes

Schizophrenia is a devastating mental disorder with disease mechanisms that are still poorly understood. Evidence has emerged that lipid dysregulations and myelination abnormalities might contribute to the pathophysiology of schizophrenia. Antipsychotic drugs often induce severe metabolic adverse effects, such as weight gain, dyslipidemias, and diabetes. However, several studies in chronic patients have indicated that some antipsychotic drug-related metabolic changes may be associated with improvements in psychotic symptoms. The main aim of this doctoral thesis was to combine clinical, biological, and imaging data to increase our current understanding of the relationship between serum lipid changes and various outcomes in antipsychotic-treated patients earlier in their illness course with emphasis on first-episode psychosis (FEP) patients. The clinical samples included FEP patients using antipsychotic drug treatment, olanzapine-treated, and unmedicated patients with broad schizophrenia spectrum disorders, along with a group of healthy controls from the Thematically Organized Psychosis project in Oslo. The participants underwent a thorough clinical evaluation, structural imaging, analyses of serum lipids, and physical examination, including assessment of body mass index (BMI). The severity of positive and negative symptoms and cognitive performances were assessed at inclusion and after a one-year follow-up, along with serum lipids. Linear mixed-effects models were used to examine associations between changes in serum lipids versus changes in positive, negative, and cognitive symptoms. General linear models were used to investigate associations between serum lipids and cortical thickness and gray/white matter intensity contrast, which were used as proxy measures for intracortical myelin. Our results indicate that an increase in serum HDL-C during antipsychotic drug treatment is associated with improvements in negative symptoms and verbal learning, independent of changes in BMI. Moreover, OLZ treatment was linked to normalized cortical intensity contrast, and a higher serum level of HDL-C in OLZ-treated patients was related to thicker cortices suggesting a lipid-mediated effect on intracortical myelin. Together, our results may indicate that the therapeutic effect of antipsychotic drug treatment could in parts be linked to lipid biosynthesis

Intracranial arachnoid cysts: impairment of higher cognitive functions and postoperative improvement

Background Intracranial arachnoid cysts have been shown to yield cognitive impairment over a range of basic mental functions, and these functions normalize after surgical cyst decompression. We wanted to investigate whether such cysts may also impair executive cognitive functions, and whether surgical cyst decompression leads to an improvement. Methods This study included 22 patients with arachnoid cysts and 13 control patients scheduled for low back surgery. All subjects were tested with Delis-Kaplan Executive Function System (D-KEFS) tests, assessing executive function 1 day before surgery and a minimum of 3 months after surgery. The data were analyzed according to scaled score computations based on raw scores provided by D-KEFS, adjusted for age, gender, and educational norms. Results Preoperatively, the patients with cysts group performed worse than the control group in verbal knowledge, mental flexibility, inhibitory capacity, problem solving, and planning skills. Postoperatively, the patients with cysts group significantly improved performance and were no longer different from the control group in the following subtests: inhibition, inhibition/switching, letter fluency, category switching, and total switching accuracy. The patients with cysts group also significantly improved performance in color naming, category fluency, and in the Tower test, but nevertheless remained impaired at follow-up compared with the control group. The control group did not show a similar improvement, except for the Tower test. Cyst size or postoperative volume reduction did not correlate with cognitive performance or postoperative improvement. Patients with left-sided temporal cysts performed poorer than patients with right-sided cysts on a complex verbal task demanding mental flexibility. Conclusions Arachnoid cysts seem to impair not only basic cognition, but also executive functions. Most of this impairment appears to be reversible after surgical cyst decompression. These results may have implications for future preoperative considerations for patients with intracranial arachnoid cysts

Sex-Specific Effect of Serum Lipids and Body Mass Index on Psychotic Symptoms, a Cross-Sectional Study of First-Episode Psychosis Patients

Background: Schizophrenia is a disorder with considerable heterogeneity in course and outcomes, which is in part related to the patients' sex. Studies report a link between serum lipids, body mass index (BMI), and therapeutic response. However, the role of sex in these relationships is poorly understood. In a cross-sectional sample of first-episode psychosis (FEP) patients, we investigated if the relationship between serum lipid levels (total cholesterol, HDL-C, LDL-C, and triglycerides), BMI, and symptoms differs between the sexes. Methods: We included 435 FEP patients (males: N = 283, 65%) from the ongoing Thematically Organized Psychosis (TOP) study. Data on clinical status, antipsychotics, lifestyle, serum lipid levels, and BMI were obtained. The Positive and Negative Syndrome Scale (PANSS) and the Calgary Depression Scale for Schizophrenia (CDSS) were used to assess psychotic and depressive symptoms. General linear models were employed to examine the relationship between metabolic variables and symptomatology. Results: We observed a female-specific association between serum HDL-C levels and negative symptoms (B = −2.24, p = 0.03) and between triglycerides levels (B = 1.48, p = 0.04) and BMI (B = 0.27, p = 0.001) with depressive symptoms. When controlling for BMI, only the association between serum HDL-C levels and negative symptoms remained significant. Moreover, the HDL-C and BMI associations remained significant after controlling for demography, lifestyle, and illness-related factors. Conclusion: We found a relationship between metabolic factors and psychiatric symptoms in FEP patients that was sex-dependent

Sex-Specific Effect of Serum Lipids and Body Mass Index on Psychotic Symptoms, a Cross-Sectional Study of First-Episode Psychosis Patients

Background: Schizophrenia is a disorder with considerable heterogeneity in course and outcomes, which is in part related to the patients' sex. Studies report a link between serum lipids, body mass index (BMI), and therapeutic response. However, the role of sex in these relationships is poorly understood. In a cross-sectional sample of first-episode psychosis (FEP) patients, we investigated if the relationship between serum lipid levels (total cholesterol, HDL-C, LDL-C, and triglycerides), BMI, and symptoms differs between the sexes. Methods: We included 435 FEP patients (males: N = 283, 65%) from the ongoing Thematically Organized Psychosis (TOP) study. Data on clinical status, antipsychotics, lifestyle, serum lipid levels, and BMI were obtained. The Positive and Negative Syndrome Scale (PANSS) and the Calgary Depression Scale for Schizophrenia (CDSS) were used to assess psychotic and depressive symptoms. General linear models were employed to examine the relationship between metabolic variables and symptomatology. Results: We observed a female-specific association between serum HDL-C levels and negative symptoms (B = −2.24, p = 0.03) and between triglycerides levels (B = 1.48, p = 0.04) and BMI (B = 0.27, p = 0.001) with depressive symptoms. When controlling for BMI, only the association between serum HDL-C levels and negative symptoms remained significant. Moreover, the HDL-C and BMI associations remained significant after controlling for demography, lifestyle, and illness-related factors. Conclusion: We found a relationship between metabolic factors and psychiatric symptoms in FEP patients that was sex-dependent

Lifetime Cannabis Use Is Not Associated With Negative Beliefs About Medication in Patients With First Treatment Psychosis

Objective: Cannabis use is common among patients with psychosis, and along with negative beliefs about medication, it has been found to predict poor adherence to antipsychotic drug treatment. Such lack of adherence to antipsychotic drug treatment increases the risk of poor clinical outcomes and relapse in patients with first treatment for psychosis (FTP). However, to date, it is unclear whether cannabis use may be related to negative perceptions about antipsychotic drug treatment. Methods: A cross-sectional sample of 265 FTP patients with schizophrenia spectrum disorder underwent extensive clinical assessments. Three measures of cannabis use were obtained: lifetime, current and meeting diagnostic criteria for abuse or addiction. For the primary analyses we focused on lifetime cannabis use. The Beliefs about Medication Questionnaire (BMQ) was employed to assess the patients' specific concerns and perceptions of antipsychotic medications, as well as general beliefs about pharmacotherapy. The relationship between lifetime cannabis use and BMQ scores was investigated with general linear model (GLM) analyses, controlling for age and sex. Results: Patients with lifetime use of cannabis ≥10 times were more likely to be male, younger at the age of onset of psychosis and with higher levels of alcohol use and daily tobacco smoking, as compared to the non-users (p < 0.05). Neither lifetime use of cannabis, current use nor a cannabis abuse diagnosis was associated with negative beliefs about medicines as measured by the BMQ questionnaire. Conclusion: Use of cannabis is not linked to negative perceptions about antipsychotic medicines in patients with FTP. Other reasons for poor compliance to antipsychotic drug treatment in cannabis users need to be further investigated