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Background: The neuroinflammatory hypothesis of Major Depressive Disorder (MDD) postulates that dysregulated cytokine production is implicated in the etiopathology of the disorder. This study aimed to determine baseline levels of Interleukin-8 (IL-8), an inflammatory cytokine, in MDD and identify possible changes in response to antidepressant drug therapy. Methods: Two independent groups of MDD patients who met study criteria were enrolled; one group was treated with Escitalopram and the other with Quetiapine for twelve weeks. There was a healthy control (HC) group. In the Escitalopram group 30 patients completed the baseline visit and in the Quetiapine group 43 patients. Plasma concentrations of IL-8 were measured at baseline, week eight, and week 12 of treatment. IL-8 levels were correlated with depression severity at baseline and week 12. The sample size for IL-8 analysis was 17 study completers in the Escitalopram study, 21 study completers in the Quetiapine study, and 19 HCs. We used the Student's t-test and the Pearson Correlation Coefficient for statistical analyses. Results: MDD patients exhibited elevated IL-8 levels at baseline compared to healthy controls (p = 0.007). However, IL-8 levels did not show a significant reduction after 12 weeks of treatment and were not significantly correlated with depression severity at either baseline or week 12 of treatment. However, there was a notable downtrend in IL-8 levels after treatment in both groups though not statistically significant. Limitations: Study limitations include sample size variations and power, and study length. No formal assessment was conducted to rule out Axis II diagnoses. Conclusions: These findings underscore the relationship between IL-8 and MDD, suggesting that IL-8 may play a role in the pathophysiology of MDD, but its relationship with antidepressant treatment requires a prolonged period of treatment. This study suggests a role for IL-8 in MDD as a pro-inflammatory biomarker, while the lack of immediate normalization post-treatment indicates the need for further exploration of delayed effects of antidepressant therapy on immune markers and IL-8′s relationship with the mechanism of action of specific pharmacotherapies used in MDD.

Interleukin-8 (IL-8/CXCL8), an essential CXC chemokine, significantly influences psychoneuroimmunological processes and affects neurological and psychiatric health. It exerts a profound effect on immune cell activation and brain function, suggesting potential roles in both neuroprotection and neuroinflammation. IL-8 production is stimulated by several factors, including reactive oxygen species (ROS) known to promote inflammation and disease progression. Additionally, CXCL8 gene polymorphisms can alter IL-8 production, leading to potential differences in disease susceptibility, progression, and severity across populations. IL-8 levels vary among neuropsychiatric conditions, demonstrating sensitivity to psychosocial stressors and disease severity. IL-8 can be detected in blood circulation, cerebrospinal fluid (CSF), and urine, making it a promising candidate for a broad-spectrum biomarker. This review highlights the need for further research on the diverse effects of IL-8 and the associated implications for personalized medicine. A thorough understanding of its complex role could lead to the development of more effective and personalized treatment strategies for neuropsychiatric conditions.

Background: Mitochondria are involved in energy production, oxidative balance, cell survival/apoptosis, immune response, and inflammation. A possible role in affective disorders has fueled research on mitochondrial targets for novel treatments. Methods: A systematic review of the literature was conducted, in Science Direct, Scopus and PubMed databases, from inception to 12th September 2022. Key words used were mitochondria AND/OR inflammation AND affective OR bipolar OR depression AND therapy OR treatment OR intervention. Results: Twenty-one studies were included in the analysis. Animal studies (n=16) have shown positive results for Nucleus Accumbens Deep Brain Stimulation (NAc DBS), Near-Infrared Photobiomodulation (NIR-PBM), exercise, 48-hour fasting, and fluoxetine, Li, valproate, BI-11A7 Bid inhibitor, methylene blue (MB), AC-5216, atractylenolide-III (ALT-III), ONO-2952, oxytocin (OT), tocopherol-a, Coenzyme Q10 (CoQ10). Human studies (n=5) have tested adjunctive therapies, with NAC plus antioxidant combination therapy, triacetyl-uridine (TAU), cytidine add-on, and andacetyl-l-carnitine and a-lipoic acid combination, with positive (TAU), negative, or difficult-to-interpret results. Limitations: The search was conducted on three databases only, and only articles written in English were included. Unpublished articles or research with negative results may have been missed. Conclusion: Mitochondria-targeting interventions are promising novel treatments for depression and bipolar disorder.

Depression is one of the most common mental disorders. Despite its high prevalence, the etiopathogenesis of depression is not yet fully understood. Only around 1/3 of depressed patients remit in response to standard antidepressant treatment. Hence further studies are needed to search for potential pathomechanisms leading to depression and thereby identify novel biological targets for antidepressant therapies. The aim of this review paper is to explain the potential role of interleukin-17 in the pathogenesis of depression in the context of the inflammation hypothesis of this disorder. In this paper, we present a literature review of interleukin 17 (IL-17) blood levels in patients with depressive disorders and discuss potential pathomechanisms linking this cytokine to the development of depression.

Background: Affective illness has been associated with a proinflammatory state, and it is generally accepted that the immune system plays a key role in the pathophysiology of mood disorders. Since inflammatory biomarkers are elevated in bipolar disorder, anti-inflammatory combination therapies may enhance response and reverse treatment resistance. Purpose: In the present study we investigated the possible impact of single nucleotide polymorphisms (SNPs) within the CRP gene on CRP blood levels, treatment response and level-of-stress perception in our cohort of treatment-resistant bipolar-depressed patients receiving escitalopram and celecoxib, or escitalopram and placebo, as previously reported (Halaris et al., 2020). Methods: Study design, clinical findings, and CRP blood levels have been reported previously (Halaris et al., 2020; Edberg et al., 2018). In this follow-up study we extracted DNA from blood cells collected at baseline. Genome-wide genotyping was performed for all subjects using the Infinium Multi-Ethnic Global-8 v1.0 Kit. Based on reports in the literature indicating possible associations with psychiatric conditions, ten previously reported CRP gene polymorphisms were evaluated in a preliminary analysis. We focused on rs3093059 and rs3093077 were in complete LD. Carriers were defined as those possessing at least one C allele for rs3093059, or at least one G allele for rs3093077. Additionally, we determined blood levels of the medications administered. Results: Non-carriers of rs3093059 and rs3093077 had significantly lower baseline CRP blood levels than carriers (p = 0.03). Increased rates of HAM-D17 response (p = 0.21) and remission (p = 0.13) and lower PSS-14 scores (p = 0.13) were observed in non-carriers among subjects receiving celecoxib but they did not reach statistical significance. When examining all subjects, nominally significant associations between carrier-status and remission (p = 0.04) and PSS-14 scores (p = 0.04) were observed after correcting for treatment arm. Non-carriers receiving celecoxib had the highest rates of response and remission, and the lowest stress scores. Conclusions: Carriers of the CRP SNPs may have higher baseline CRP levels, although non-carriers appear to benefit more from celecoxib co-therapy. Determination of the carrier status in conjunction with pretreatment blood CRP level measurement may contribute to personalized psychiatric practice, but replication of the present findings is needed.

Bipolar Disorder (BD) is a multi-faceted and recurring lifelong psychiatric illness characterized by an alternating course of manic or hypomanic and depressive episodes. A feature of BD, much like in major depressive disorder, is treatment resistance. Treatment resistant bipolar depression (TRBDD) is defined as “failure to reach sustained symptomatic remission for 8 consecutive weeks after two separate treatment trials, at adequate therapeutic doses and treatment exposure. At least in a subset of TRBDD subjects, an underlying metabolic and immunologic dysregulation has been postulated. It is generally accepted that the immune system plays a key role in the pathophysiology of mood disorders. Inflammatory biomarkers are elevated in BDD, therefore anti-inflammatory combination therapy may enhance response to treatment and reverse treatment resistance. Cyclooxygenase-2 (COX-2) is an enzyme that is expressed in the central nervous system, and plays an important functional role in the brain and periphery. COX-2 regulates the CNS immune system via the effects of prostaglandins. The products of this enzyme mediate the inflammatory response. Patients with a depressive disorder, may have increased blood levels of C-Reactive Protein (CRP) and this may be a key contributor to TRD. In this study, we investigated whether reducing pro-inflammatory mediators, such as CRP, would reduce resistance and augment the therapeutic response. Baseline elevations of CRP were noted in TRBDD patients compared to Healthy Control (HC) subjects. Therefore, CRP may prove to be a useful biomarker for TRBDD. Additionally, we investigated the possible impact of single nucleotide polymorphisms (SNPs) within the CRP gene on CRP blood levels, treatment response, and level of stress perception. Non-carriers had significantly lower baseline CRP blood levels. CRP SNPs were associated with increased baseline CRP levels in all subjects. The CRP SNP non-carriers trended for lower stress scores, better response and more remissions in subjects taking celecoxib. Carriers of the CRP SNPs may have higher baseline CRP levels, and may benefit more from adjunctive celecoxib antidepressant therapy.

Background: in a recent double-blind, placebo controlled RCT we demonstrated that selective inhibition of cyclo-oxygenase 2 (COX2) is an effective adjunctive strategy in treatment-resistant bipolar depression (TRBDD). To better clarify the mechanisms underlying TRBDD and treatment response, we conducted a retrospective exploratory analysis of the systemic inflammatory response index (SIRI = absolute neutrophils × absolute monocytes/absolute lymphocytes) in relation to other biomarkers and clinical outcomes after escitalopram (ESC), combined with the COX-2 inhibitor, celecoxib (CBX), versus placebo. Methods: Baseline measures of SIRI were compared between TRBDD and healthy controls (HC), and correlated with blood-based inflammatory cytokines, kynurenines, and growth factors. Post-treatment Hamilton Depression Rating Scale 17 (HAMD-17) total scores (clinical outcome) were modelled according to SIRI adjusting for demographics (including relevant interactions with SIRI), baseline depression, treatment arm, and treatment timepoint using multiple linear regression and robust linear mixed effects models. Results: Baseline SIRI did not distinguish TRBDD from HC groups. Baseline SIRI was significantly correlated with lower baseline MCP-1. The relationship between SIRI and HAMD-17 was significant at treatment week 8, in contrast to baseline. Finally, baseline SIRI predicted elevated post-treatment HAMD-17 scores, amongst patients with elevated depression scores at baseline. Significance: High pre-treatment SIRI may predict poorer depressive outcomes amongst TRBDD patients with baseline elevated depression.

Brain-Derived Neurotrophic Factor (BDNF) is crucial for various aspects of neuronal development and function, including synaptic plasticity, neurotransmitter release, and supporting neuronal differentiation, growth, and survival. It is involved in the formation and preservation of dopaminergic, serotonergic, GABAergic, and cholinergic neurons, facilitating efficient stimulus transmission within the synaptic system and contributing to learning, memory, and overall cognition. Furthermore, BDNF demonstrates involvement in neuroinflammation and showcases neuroprotective effects. In contrast, BDNF antisense RNA (BDNF-AS) is linked to the regulation and control of BDNF, facilitating its suppression and contributing to neurotoxicity, apoptosis, and decreased cell viability. This review article aims to comprehensively overview the significance of single nucleotide polymorphisms (SNPs) in BDNF/BDNF-AS genes within psychiatric conditions, with a specific focus on their associations with depression, schizophrenia, and bipolar disorder. The independent influence of each BDNF/BDNF-AS gene variation, as well as the interplay between SNPs and their linkage disequilibrium, environmental factors, including early-life experiences, and interactions with other genes, lead to alterations in brain architecture and function, shaping vulnerability to mental health disorders. The potential translational applications of BDNF/BDNF-AS polymorphism knowledge can revolutionize personalized medicine, predict disease susceptibility, treatment outcomes, and guide the selection of interventions tailored to individual patients.

It is well-established that cardiovascular disease and depression are highly comorbid. This study aimed to assess the possible role of the NOD-like receptor protein 3 (NLRP3) inflammasome pathway and the high-sensitivity C-reactive protein (hsCRP) in patients with incident myocardial infarction in the presence or absence of depression. Sixty-eight consecutive patients with incident ST-elevation myocardial infarction and twenty healthy subjects were included. The patients were assessed using the Structured Clinical Interview for DSM-5 Disorders—Clinician Version during their 1–4-day-long hospitalization and were divided into two groups: with and without comorbid depression. Blood samples for the determination of NLRP3, interleukin-18 (IL-18), interleukin-1β (IL-1β), and hsCRP levels were analyzed using ELISA. NLRP3, IL-1β, IL-18, and hsCRP levels were significantly higher in myocardial infarction patients compared to the healthy group (p = 0.02, p < 0.001, p < 0.001, and p < 0.001, respectively). No significant difference was found between the myocardial groups with and without depression. However, in the logistic regression analysis, the NLRP3 variable in myocardial infarction patients was found to have a significant contribution to the likelihood of depression (p = 0.015, OR = 1.72, and CI = 1.11–2.66). The likelihood of depression is associated with increasing NLRP3 levels in myocardial infarction patients. However, this potential role should be further explored in a larger sample.

(1) Background: Inflammation is associated with depressive illness and treatment resistance. This study assessed a novel inflammatory index, the Systemic Immune-Inflammation Index (SII), in patients diagnosed with treatment-resistant bipolar depression (TRBDD) before and after treatment with escitalopram (ESC) and celecoxib (CBX) add-on or ESC and placebo (PBO), and compared them to healthy control (HC) subjects. (2) Methods: This is a secondary biological analysis from a double-blind randomized placebo-controlled trial of CBX augmentation in TRBDD. Our subsample with available complete blood count (CBC) data included 52 TRBDD subjects, randomized into an ESC + CBX, (n = 29), an ESC + PBO arm (n = 23), and an HC group (n = 32). SII was calculated from the CBC with differential (SII = platelets x neutrophils/lymphocytes) at baseline and end of treatment (8 weeks). Blood inflammation biomarkers, growth factors, and kynurenine metabolites were determined at both timepoints. Depressive symptom severity was the primary outcome, using the HAMD-17 rating scale score to quantitate treatment response and remission rates. (3) Results: Baseline SII did not discriminate TRBDD from HC, nor was it associated with HAMD-17 score at any timepoint, although it was significantly associated with lower baseline VEGF (p = 0.011) and higher week 8 levels of IL1-β (p = 0.03) and CRP (p = 0.048). Post-treatment HAMD-17 was not independently predicted using baseline SII unless an interaction with age was present (p = 0.003 was included), even after relevant adjustments. A similar effect was seen with baseline neutrophils. (4) Conclusions: While SII was not an independent predictor of treatment outcome, elevated baseline SII was a predictor of poor treatment response amongst older patients with TRBDD.

Depressive disorders are characterized by persistent low mood, loss of interest and pleasure, decreased energy, varying levels of social and occupational dysfunction. Depressive symptoms include depressed mood, anhedonia, appetite disturbances and changes in weight, loss of libido, sleep disturbances, lack of energy, unwarranted guilt, difficulty in concentration, and even suicidal ideation and intent. Major depressive disorder (MDD) is characterized by the presence of at least five of the abovementioned symptoms during the same two-week period with a change from previous functioning. Depressed mood and/or loss of interest/pleasure must be present and can be further classified from mild to severe (American Psychiatric Association, 2013). MDD can negatively impact a person's life and affects 264 million people globally (GBD, 2018). There is a large body of evidence that many MDD patients have an increased level of inflammation, as indicated by elevated levels of C-reactive protein (CRP) and other proinflammatory biomarkers. CRP is an acute phase reactant produced by the liver in response to infections, inflammatory conditions in the body and stress. CRP has at least two structural isoforms, monomeric and pentameric, and serves as both a proinflammatory and anti-inflammatory protein, depending on the isoform. There is also evidence that polymorphisms within the CRP gene influence the levels of CRP produced. The objective of this review is to highlight current research on the relationship of CRP with MDD, the genetics of CRP, and the possible relationship of CRP structural isoforms specifically in the diagnosis, pathology, and treatment of MDD.

Aim. To determine the efficacy and safety of vitamin D3 supplementation in reducing depressive symptoms in women with type 2 diabetes (T2D), depression, and low vitamin D. Methods. In this double-blind randomized active comparator-controlled trial, women with significant depressive symptoms as assessed by the Center for Epidemiologic Studies Depression (CES-D) scale received weekly oral vitamin D3 supplementation (50,000 IU) or an active comparator (5,000 IU) for 6 months. Assessments of vitamin D, 25-hydroxyvitamin D [25 (OH) D], and depression were measured at baseline, 3 months, and 6 months. Results. A total of 129 women were randomized, from which 119 completed the study (57 in lower dose and 62 in higher dose). Participants had an average 25 (OH) D and HbA1c of 20.8 ng/mL and 7.8%, respectively, at baseline. They were diverse (48% Black) and had a mean age of 50 and T2D for about 8 years. Upon completion of vitamin D3 supplementation, serum 25 (OH) D levels increased with 50,000 IU (+34 ng/mL) and 5,000 IU (+10 ng/mL). There was no difference in CES-D scores by treatment dose. Overall, depressive symptoms significantly improved over time with an average CES-D decline of 12.98 points (95% CI: −15.04 to −10.93; p

Background: Inflammation plays a pivotal role in the etiopathology of Major Depressive Disorder (MDD), at least in a subset of patients. It is crucial to first establish which specific inflammatory biomarkers are of clinical utility. Anti-cardiolipin antibody (aCL IgM) is an inflammatory marker that has the potential to be such a candidate but there are insufficient studies to confirm this potential. Objective: To investigate the baseline titer level and the longitudinal progression of plasma titers of aCL IgM in MDD subjects receiving antidepressant therapy in comparison to healthy control (HC) subjects; to determine if changes in aCL IgM plasma titers correlate to changes in depressive symptoms; and, to ascertain if baseline aCL IgM plasma titers could predict treatment response. Methods: Forty-eight medically healthy outpatients diagnosed with MDD were enrolled in one of two groups in two sequentially conducted clinical trials. In Group-E, patients received a 12-week regimen of escitalopram (n = 20). Those in Group-Q received a 12-week regimen of quetiapine (n = 28). The main outcome measure was plasma aCL IgM titers, the Hamilton Rating Scale for Depression (HAM-D17) and the Hamilton Rating Scale for Anxiety (HAM-A). There were 16 HC subjects. Results: When Group-Q and Group-E participants were grouped together (n = 48), MDD subjects had an elevated baseline aCL IgM (19.9 μg/mL) compared to HC subjects (8.32 μg/mL) (p = 0.006). aCL IgM correlated significantly with HAM-D17 scores at baseline in MDD subjects (p = 0.0185, r = 0.296). Examining the individual groups, Group-Q MDD patients had a significantly elevated baseline aCL IgM (p = 0.008) while Group-E’s MDD patients did not. On the other hand, only Group-E MDD patients showed a significant correlation at baseline between aCL IgM and HAM-A score (p = 0.0392, r = 0.4327); they also showed a significant inverse correlation between week 12 HAMD-17 Item #10 (Anxiety, Psychic) and week 12 aCL IgM titer (p = 0.0268, r = −0.5516). Conclusions: MDD patients had significantly higher plasma titers of aCL IgM when compared to HC subjects. Moreover, at baseline, the higher the aCL IgM titer, the higher the depression severity, as measured by HAMD-17 score. However, this study did not demonstrate that aCL IgM titers changed significantly throughout a 12-week course of antidepressant treatment and revealed no correlation between changes in depressive symptoms and changes in aCL IgM titers. Baseline aCL IgM could not predict treatment response. We conclude that, despite lacking predictive ability as regards treatment response, plasma titers of aCL IgM have a diagnostic potential in MDD that necessitates further exploration.

Background: Adjunctive inflammatory treatments improve response and remission rates in treatment-resistant bipolar depression (TRBDD), but underlying mechanisms remain unclear. Given the association between hypothalamic-pituitary-adrenal (HPA) axis dysregulation and treatment-resistant depression, we investigated the pre-treatment HPA-axis profile in relation to treatment response. Methods: This is a secondary analysis of 31 TRBDD patients with moderately severe depression scores as assessed with the Hamilton Depression Rating Scale 17 (HAMD17), who were randomized to receive either escitalopram (ESC) (10–40 mg daily) + celecoxib (CBX) (200 mg twice daily), or ESC (10–40 mg daily) + placebo (PBO) (twice daily). Salivary cortisol was measured at baseline. A multivariate linear regression model was applied to evaluate whether depression scores at Week 8 were related to CBX and baseline salivary cortisol, adjusting for sex, age, BMI, and baseline depression scores. We utilized the HAMD17 and Montgomery-Asberg Depression Rating Scale (MADRS). Results: Coefficient of determination (R2) for week 8 MADRS and HAMD17 scores were 0.907 and 0.624 (both p-value

Background: Taking into account the role of oxidative stress in neurodegeneration, we sought to evaluate the expression of genes for select enzymes with antioxidant properties (paraoxonases PON1, PON2 and PON3 and myeloperoxidase MPO) at the mRNA and protein levels in patients with depressive disorders. We further sought to determine the impact of oxidative stress in the etiopathogenesis of this group of mood disorders. Methods: A total of 290 subjects (190 depressed patients, 100 healthy controls) took part in the study. Sociodemographic and clinical data were collected. The severity of depressive symptoms was assessed using the Hamilton Depression Rating Scale (HDRS). Venous blood was collected. RT-PCR was used to assess gene expression at the mRNA level, while enzyme-linked immunosorbent assay (ELISA) was used to assess gene expression at the protein level. Results: The expression of the PON2 and PON3 genes at the protein level was significantly higher in depressive patients than in healthy controls. mRNA expression of the PON1, PON2 and PON3 genes was slightly higher in patients with depressive disorders than in the control group, however, this relationship was not statistically significant. On the other hand, the expression of the MPO gene at both mRNA and protein levels was significantly lower in patients with depressive disorder than in the control group. Conclusions: Our results are not in agreement with many studies on enzymes involved in maintaining oxidative balance. Our findings may not support the utility of paraoxonases (PON) or myeloperoxidase (MPO) as promising biomarker candidates of depression pending larger and well controlled studies.

(1) Background: Only 60–70% of depressed patients respond to standard antidepressant treatments. Hence, it is essential to search for new, effective and safe therapies for unmet clinical needs of treatment-resistant depression (TRD). Agents targeting the components of the JAK-STAT signaling pathway have been shown to be relevant in immunology and are commonly used in the treatment of many hematological, rheumatological and dermatological diseases. The aim of this study was to investigate the role of elements of the JAK-STAT signaling pathway in the etiopathogenesis of depressive disorders. (2) Methods: A total of 290 subjects took part in the study (190 depressed patients, 100 healthy controls). Sociodemographic data were collected. The severity of depressive symptoms was assessed using the Hamilton Depression Rating Scale (HDRS). The gene expression at the mRNA protein levels of JAK (JAK1-JAK3) and STAT (STAT1-STAT5) was assessed by using RT-PCR and ELISA. (3) Results: Increased expression of JAK3 and decreased expression of STAT1 were observed in the group of depressed patients. (4) Conclusions: Further studies are necessary to determine whether moderation of the JAK-STAT signaling pathways is involved in the treatment of depression.

Pharmacogenomic (PGx) testing is being increasingly recognized by clinicians as an essential tool to guide medication decisions for treatment of psychiatric illnesses. Extensive implementation of PGx testing, however, varies by setting and location. In this retrospective study, we reviewed charts from 592 patients diagnosed with a psychiatric disorder at the Loyola University Medical Center, for whom PGx testing was performed. Information collected included demographics at the time of testing, psychiatric diagnosis, medical and psychiatric history and medications prior and after PGx testing. Of the 592 charts analyzed, the most common primary diagnoses were depression (52%) and anxiety (12%). Prior to PGx testing, 72% of patients were prescribed three or more medications, whereas, after testing, only 44% were prescribed three or more medications included in the test panel (p < 0.0001). The most common clinical consideration on the PGx reports was recommendation to reduce dosages (33%). After PGx testing, the proportion of patients taking incongruent medications decreased from 26% to 19% and that of patients taking congruent medications increased from 74% to 81% (p = 0.006). The results from this retrospective data analysis demonstrated a reduction in polypharmacy and an increase in recommendation-congruent medication prescribing resulting from implementation of PGx testing.

Major Depressive Disorder (MDD) is a highly prevalent psychiatric disorder worldwide. It causes individual suffering, loss of productivity, increased health care costs and high suicide risk. Current pharmacologic interventions fail to produce at least partial response to approximately one third of these patients, and remission is obtained in approximately 30% of patients. This is known as Treatment-Resistant Depression (TRD). The burden of TRD exponentially increases the longer it persists, with a higher risk of impaired functional and social functioning, vast losses in quality of life and significant risk of somatic morbidity and suicidality. Different approaches have been suggested and utilized, but the results have not been encouraging. In this review article, we present new approaches to identify and correct potential causes of TRD, thereby reducing its prevalence and with it the overall burden of this disease entity. We will address potential contributory factors to TRD, most of which can be investigated in many laboratories as routine tests. We discuss endocrinological aberrations, notably, hypothalamic-pituitary-adrenal (HPA) axis dysregulation and thyroid and gonadal dysfunction. We address the role of Vitamin D in contributing to depression. Pharmacogenomic testing is being increasingly used to determine Single Nucleotide Polymorphisms in Cytochrome P450, Serotonin Transporter, COMT, folic acid conversion (MTHFR). As the role of immune system dysregulation is being recognized as potentially a major contributory factor to TRD, the measurement of C-reactive protein (CRP) and select immune biomarkers, where testing is available, can guide combination treatments with anti-inflammatory agents (e.g., selective COX-2 inhibitors) reversing treatment resistance. We focus on established and emerging test procedures, potential biomarkers and non-biologic assessments and interventions to apply personalized medicine to effectively manage treatment resistance in general and TRD specifically.

Autonomic nervous system (ANS) dysregulation in depression is associated with symptoms associated with the ANS. The beat-to-beat pattern of heart rate defined as heart rate variability (HRV) provides a noninvasive portal to ANS function and has been proposed to represent a means of quantifying resting vagal tone. We quantified HRV in bipolar depressed (BDD) patients as a measure of ANS dysregulation seeking to establish HRV as a potential diagnostic and prognostic biomarker for treatment outcome. Forty-seven BDD patients were enrolled. They were randomized to receive either escitalopram–celecoxib or escitalopram-placebo over 8 weeks in a double-blind study design. Thirty-five patients completed the HRV studies. Thirty-six healthy subjects served as controls. HRV was assessed at pretreatment and end of study and compared with that of controls. HRV was quantified and corrected for artifacts using an algorithm that incorporates time and frequency domains to address non-stationarity of the beat-to-beat heart rate pattern. Baseline high frequency-HRV (i.e., respiratory sinus arrhythmia) was lower in BDD patients than controls, although the difference did not reach significance. Baseline low-frequency HRV was significantly lower in BDD patients (ln4.20) than controls (ln = 5.50) (p

Lubomira Izáková1, Ivan Andre1, Angelos Halaris21Psychiatric Clinic, Faculty of Medicine Comenius University and Faculty Hospital, Bratislava, Slovakia; 2Department of Psychiatry and Behavioral Neurosciences, Loyola University Medical Center, Maywood, IL, USAAbstract: Several studies have demonstrated the effectiveness of adjunctive antidepressant drug therapy to improve the depressive or negative symptoms of schizoaffective disorder, however, monotherapy with atypical antipsychotics may be advantageous. We compared the efficacy and safety of risperidone monotherapy versus combination therapy of haloperidol with sertaline for the acute treatment of schizoaffective disorder, depressed type. This is an open label study of 52 female inpatients randomly assigned to risperidone alone (N = 26) or haloperidol in combination with sertraline (N = 26) for 12 weeks. The mean daily doses of medications were: risperidone: 3.75–3.29 mg/day, haloperidol: 5.35–4.15 mg/day, sertraline: 65.39–133.82 mg/day. Efficacy was measured using clinical rating scales of treatment, safety, and tolerability. Risperidone patients showed statistically significant greater improvement than haloperidol-sertraline patients on efficacy measures including Positive and Negative Syndrome Scale and Clinical Global Impressions rating. A higher number of risperidone patients dropped out of the study early. Fewer adverse events and lesser need for concomitant medications occurred in patients on risperidone. The risperidone group showed better psychological, social and occupational functioning (Global Assessment of Functioning) and higher quality of life (Heinrich’s Quality of Life Scale). Risperidone has higher antipsychotic efficacy and tolerability compared with haloperidol-sertraline combination for the acute treatment of schizoaffective disorder, depressed type. Both treatments were comparable in terms of antidepressant efficacy.Keywords: schizoaffective disorder, depressed type, risperidone, haloperidol, sertraline

List of abstracts and authors: 1. Antipsychotics in anxiety disorders Christer Allgulander 2. Anxiety in somatic disorders Christer Allgulander 3. Community rehabilitation of the schizophrenic patient Orlando Alonso Betancourt, Maricela Morales Herrera 4. Dual diagnosis: A theory-driven multidisciplinary approach for integrative care David Blackbeard 5. The emotional language of the gut - when 'psyche' meets 'soma' Helen Clark 6. The Psychotherapy of bipolar disorder Franco Colin 7. The Psychotherapy of bipolar disorder Franco Colin 8. Developing and adopting mental health policies and plans in Africa: Lessons from South Africa, Uganda and Zambia Sara Cooper, Sharon Kleintjes, Cynthia Isaacs, Fred Kigozi, Sheila Ndyanabangi, Augustus Kapungwe, John Mayeya, Michelle Funk, Natalie Drew, Crick Lund 9. The importance of relapse prevention in schizophrenia Robin Emsley 10. Mental Health care act: Fact or fiction? Helmut Erlacher, M Nagdee 11. Does a dedicated 72-hour observation facility in a district hospital reduce the need for involuntary admissions to a psychiatric hospital? Lennart Eriksson 12. The incidence and risk factors for dementia in the Ibadan study of ageing Oye Gureje, Lola Kola, Adesola Ogunniyi, Taiwo Abiona 13. Is depression a disease of inflammation? Angelos Halaris 14. Paediatric bipolar disorder: More heat than light? Sue Hawkridge 15. EBM: Anova Conundrum Elizabeth L (Hoepie) Howell 16. Tracking the legal status of a cohort of inpatients on discharge from a 72-hour assessment unit Bernard Janse van Rensburg 17. Dual diagnosis units in psychiatric facilities: Opportunities and challenges Yasmien Jeenah 18. Alcohol-induced psychotic disorder: A comparative study on the clinical characteristics of patients with alcohol dependence and schizophrenia Gerhard Jordaan, D G Nel, R Hewlett, R Emsley 19. Anxiety disorders: the first evidence for a role in preventive psychiatry Andre F Joubert 20. The end of risk assessment and the beginning of start Sean Kaliski 21. Psychiatric disorders abd psychosocial correlates of high HIV risk sexual behaviour in war-effected Eatern Uganda E Kinyada, H A Weiss, M Mungherera, P Onyango Mangen, E Ngabirano, R Kajungu, J Kagugube, W Muhwezi, J Muron, V Patel 22. One year of Forensic Psychiatric assessment in the Northern Cape: A comparison with an established assessment service in the Eastern Cape N K Kirimi, C Visser 23. Mental Health service user priorities for service delivery in South Africa Sharon Kleintjes, Crick Lund, Leslie Swartz, Alan Flisher and MHaPP Research Programme Consortium 24. The nature and extent of over-the-counter and prescription drug abuse in cape town Liezl Kramer 25. Physical health issues in long-term psychiatric inpatients: An audit of nursing statistics and clinical files at Weskoppies Hospital Christa Kruger 26. Suicide risk in Schizophrenia - 20 Years later, a cohort study Gian Lippi, Ean Smit, Joyce Jordaan, Louw Roos 27.Developing mental health information systems in South Africa: Lessons from pilot projects in Northern Cape and KwaZulu-Natal Crick Lund, S Skeen, N Mapena, C Isaacs, T Mirozev and the Mental Health and Poverty Research Programme Consortium Institution 28. Mental health aspects of South African emigration Maria Marchetti-Mercer 29. What services SADAG can offer your patients Elizabeth Matare 30. Culture and language in psychiatry Dan Mkize 31. Latest psychotic episode Povl Munk-Jorgensen 32. The Forensic profile of female offenders Mo Nagdee, Helmut Fletcher 33. The intra-personal emotional impact of practising psychiatry Margaret Nair 34. Highly sensitive persons (HSPs) and implications for treatment Margaret Nair 35. Task shifting in mental health - The Kenyan experience David M Ndetei 36. Bridging the gap between traditional healers and mental health in todya's modern psychiatry David M Ndetei 37. Integrating to achieve modern psychiatry David M Ndetei 38. Non-medical prescribing: Outcomes from a pharmacist-led post-traumatic stress disorder clinic A Parkinson 39. Is there a causal relationship between alcohol and HIV? Implications for policy, practice and future research Charles Parry 40. Global mental health - A new global health discipline comes of age Vikram Patel 41. Integrating mental health into primary health care: Lessons from pilot District demonstration sites in Uganda and South Africa Inge Petersen, Arvin Bhana, K Baillie and MhaPP Research Programme Consortium 42. Personality disorders -The orphan child in axis I - Axis II Dichotomy Willie Pienaar 43. Case Studies in Psychiatric Ethics Willie Pienaar 44. Coronary artery disease and depression: Insights into pathogenesis and clinical implications Janus Pretorius 45. Impact of the Mental Health Care Act No. 17 of 2002 on designated hospitals in KwaZulu-Natal: Triumphs and trials Suvira Ramlall, Jennifer Chipps 46. Biological basis of addication Solomon Rataemane 47. Genetics of Schizophrenia Louw Roos 48. Management of delirium - Recent advances Shaquir Salduker 49. Social neuroscience: Brain research on social issues Manfred Spitzer 50. Experiments on the unconscious Manfred Spitzer 51. The Psychology and neuroscience of music Manfred Spitzer 52. Mental disorders in DSM-V Dan Stein 53. Personality, trauma exposure, PTSD and depression in a cohort of SA Metro policemen: A longitudinal study Ugashvaree Subramaney 54. Eating disorders: An African perspective Christopher Szabo 55. An evaluation of the WHO African Regional strategy for mental health 2001-2010 Thandi van Heyningen, M Majavu, C Lund 56. A unitary model for the motor origin of bipolar mood disorders and schizophrenia Jacques J M van Hoof 57. The origin of mentalisation and the treatment of personality disorders Jacques J M Hoof 58. How to account practically for 'The Cause' in psychiatric diagnostic classification C W (Werdie) van Staden POSTER PRESENTATIONS 59. Problem drinking and physical and sexual abuse at WSU Faculty of Health Sciences, Mthatha, 2009 Orlando Alonso Betancourt, Maricela Morales Herrera, E, N Kwizera, J L Bernal Munoz 60. Prevalence of alcohol drinking problems and other substances at WSU Faculty of Health Sciences, Mthatha, 2009 Orlando Alonso Betancourt, Maricela Morales Herrera, E, N Kwizera, J L Bernal Munoz 61. Lessons learnt from a modified assertive community-based treatment programme in a developing country Ulla Botha, Liezl Koen, John Joska, Linda Hering, Piet Ooosthuizen 62. Perceptions of psychologists regarding the use of religion and spirituality in therapy Ottilia Brown, Diane Elkonin 63. Resilience in families where a member is living with schizophreni Ottilia Brown, Jason Haddad, Greg Howcroft 64. Fusion and grandiosity - The mastersonian approach to the narcissistic disorder of the self William Griffiths, D Macklin, Loray Daws 65. Not being allowed to exist - The mastersonian approach to the Schizoid disorder of the self William Griffiths, D Macklin, Loray Daws 66. Risky drug-injecting behaviours in Cape Town and the need for a needle exchange programme Volker Hitzeroth 67. Neuroleptic malignant syndrome in adolescents in the Western Cape: A case series Terri Henderson 68. Experience and view of local academic psychiatrists on the role of spirituality in South African specialist psychiatry, compared with a qualitative analysis of the medical literature Bernard Janse van Rensburg 69. The role of defined spirituality in local specialist psychiatric practice and training: A model and operational guidelines for South African clinical care scenarios Bernard Janse van Rensburg 70. Handedness in schizophrenia and schizoaffective disorder in an Afrikaner founder population Marinda Joubert, J L Roos, J Jordaan 71. A role for structural equation modelling in subtyping schizophrenia in an African population Liezl Koen, Dana Niehaus, Esme Jordaan, Robin Emsley 72. Caregivers of disabled elderly persons in Nigeria Lola Kola, Oye Gureje, Adesola Ogunniyi, Dapo Olley 73. HIV Seropositivity in recently admitted and long-term psychiatric inpatients: Prevalence and diagnostic profile Christina Kruger, M P Henning, L Fletcher 74. Syphilis seropisitivity in recently admitted longterm psychiatry inpatients: Prevalence and diagnostic profile Christina Kruger, M P Henning, L Fletcher 75. 'The Great Suppression' Sarah Lamont, Joel Shapiro, Thandi Groves, Lindsey Bowes 76. Not being allowed to grow up - The Mastersonian approach to the borderline personality Daleen Macklin, W Griffiths 77. Exploring the internal confirguration of the cycloid personality: A Rorschach comprehensive system study Daleen Macklin, Loray Daws, M Aronstam 78. A survey to determine the level of HIV related knowledge among adult psychiatric patients admitted to Weskoppies Hospital T G Magagula, M M Mamabolo, C Kruger, L Fletcher 79. A survey of risk behaviour for contracting HIV among adult psychiatric patients admitted to Weskoppies Hospital M M Mamabolo, T G Magagula, C Kruger, L Fletcher 80. A retrospective review of state sector outpatients (Tara Hospital) prescribed Olanzapine: Adherence to metabolic and cardiovascular screening and monitoring guidelines Carina Marsay, C P Szabo 81. Reported rapes at a hospital rape centre: Demographic and clinical profiles Lindi Martin, Kees Lammers, Donavan Andrews, Soraya Seedat 82. Exit examination in Final-Year medical students: Measurement validity of oral examinations in psychiatry Mpogisheng Mashile, D J H Niehaus, L Koen, E Jordaan 83. Trends of suicide in the Transkei region of South Africa Banwari Meel 84. Functional neuro-imaging in survivors of torture Thriya Ramasar, U Subramaney, M D T H W Vangu, N S Perumal 85. Newly diagnosed HIV+ in South Africa: Do men and women enroll in care? Dinesh Singh, S Hoffman, E A Kelvin, K Blanchard, N Lince, J E Mantell, G Ramjee, T M Exner 86. Diagnostic utitlity of the International HIC Dementia scale for Asymptomatic HIV-Associated neurocognitive impairment and HIV-Associated neurocognitive disorder in South Africa Dinesh Singh, K Goodkin, D J Hardy, E Lopez, G Morales 87. The Psychological sequelae of first trimester termination of pregnancy (TOP): The impact of resilience Ugashvaree Subramaney 88. Drugs and other therapies under investigation for PTSD: An international database Sharain Suliman, Soraya Seedat 89. Frequency and correlates of HIV Testing in patients with severe mental illness Hendrik Temmingh, Leanne Parasram, John Joska, Tania Timmermans, Pete Milligan, Helen van der Plas, Henk Temmingh 90. A proposed mental health service and personnel organogram for the Elizabeth Donkin psychiatric Hospital Stephan van Wyk, Zukiswa Zingela 91. A brief report on the current state of mental health care services in the Eastern Cape Stephan van Wyk, Zukiswa Zingela, Kiran Sukeri, Heloise Uys, Mo Nagdee, Maricela Morales, Helmut Erlacher, Orlando Alonso 92. An integrated mental health care service model for the Nelson Mandela Bay Metro Stephan van Wyk, Zukiswa Zingela, Kiran Sukeri 93. Traditional and alternative healers: Prevalence of use in psychiatric patients Zukiswa Zingela, S van Wyk, W Esterhuysen, E Carr, L Gaauche