Phenotypic clustering of bipolar disorder supports stratification by lithium responsiveness over diagnostic subtypes.

INTRODUCTION: The aim of this study was to determine whether the clinical profiles of bipolar disorder (BD) patients could be differentiated more clearly using the existing classification by diagnostic subtype or by lithium treatment responsiveness. METHODS: We included adult patients with BD-I or II (N = 477 across four sites) who were treated with lithium as their principal mood stabilizer for at least 1 year. Treatment responsiveness was defined using the dichotomized Alda score. We performed hierarchical clustering on phenotypes defined by 40 features, covering demographics, clinical course, family history, suicide behaviour, and comorbid conditions. We then measured the amount of information that inferred clusters carried about (A) BD subtype and (B) lithium responsiveness using adjusted mutual information (AMI) scores. Detailed phenotypic profiles across clusters were then evaluated with univariate comparisons. RESULTS: Two clusters were identified (n = 56 and n = 421), which captured significantly more information about lithium responsiveness (AMI range: 0.033 to 0.133) than BD subtype (AMI: 0.004 to 0.011). The smaller cluster had disproportionately more lithium responders (n = 47 [83.8%]) when compared to the larger cluster (103 [24.4%]; p = 0.006). CONCLUSIONS: Phenotypes derived from detailed clinical data may carry more information about lithium responsiveness than the current classification of diagnostic subtype. These findings support lithium responsiveness as a valid approach to stratification in clinical samples.

Health behaviours of patients with affective disorders: a cross-sectional study.

BACKGROUND: Severe mental disorders, including affective disorders (AD), are associated with high rates of physical illnesses that lead to premature patient death. Excess somatic comorbidity may be partially explained by lifestyle factors. This study aimed to investigate the health behaviours (HBs) of patients with AD in comparison to the HBs of patients with type 2 diabetes (T2D) and healthy controls (HCs) and to examine associations among HBs and sociodemographic and clinical factors, subjective quality of life and health status, and health locus of control. METHODS: The sample consisted of 108 patients with AD, including 60 with bipolar disorder (BP) and 48 with unipolar disorder (UAD). Analyses included comparisons with a subgroup of AD individuals, patients with T2D and HCs matched in age and sex. The Health Behaviour Inventory was used to evaluate the overall levels of HBs and 4 HB categories. To identify independent determinants of health behaviours, a multivariate linear regression analysis was performed with factors identified as significant in bivariate analyses. RESULTS: Most AD patients had a low level of HBs (40%), followed by moderate (35%) and high levels (25%), and there were no significant differences in HBs between the BP and UAD groups. Compared with the T2D and HC groups, the AD group had a significantly lower level of overall HBs and lower levels of HBs in one of the categories. Independent predictors of overall HBs were quality of life (ß = 0.28, p < 0.001), age (ß = 0.27, p = 0.002), and depressive symptoms (ß = 0.23, p = 0.008). A total of 30% of the variance in HBs was explained. CONCLUSIONS: These findings emphasise the need for a systematic assessment of single and multiple health behaviours to provide better care for patients with AD and reduce the potential adverse effects of an unhealthy lifestyle.

Dysfunction of the Purinergic System in Bipolar Disorder.

OBJECTIVE: To verify the purinergic hypothesis of bipolar disorder (BD), we assessed the concentration of various components of the purinergic system in manic and depressed bipolar patients. METHODS: Sixty-two patients (19 male and 43 female), aged 22-69 (49 ± 14) years, with BD were studied. Twenty-three patients (9 male and 14 female) were assessed during a manic episode and subsequent remission, and 39 patients (10 male and 29 female) were investigated in a depressive episode and the following remission. Twenty-two healthy subjects (8 male and 14 female), aged 19-70 (41 ± 14) years, served as the control group (CG). The severity of symptoms was evaluated using the Hamilton Depression Rating Scale (HDRS) and the Young Mania Rating Scale (YMRS). The concentrations of uric acid (UA) were estimated by the uricase-based method, whereas xanthine dehydrogenase (XDH), adenosine (Ado), and adenosine deaminase (ADA) by ELISA. RESULTS: The mean score in the acute episode was 32 ± 8 points in the YMRS for mania and 31 ± 8 in the HDRS for depression. UA levels were significantly higher in female bipolar patients compared to the females in the CG. The concentrations of XDH, Ado, and ADA were significantly lower in bipolar patients both during an acute episode and remission compared to CG. CONCLUSIONS: A significant dysfunction of the purinergic system in patients with BD was observed. In most instances, the disturbances were not different in the acute episode than in remission what qualifies them as trait dependent. The results may confirm the role of the purinergic system in the pathogenesis of BD.

Speech Understanding in Manic and Depressive Episodes of Mood Disorders.

OBJECTIVE: The aim of this study was to assess the perception of speech in adverse acoustic conditions during manic and depressive episodes of mood disorders. METHODS: Forty-three patients with bipolar disorder (mania, N=20; depression, N=23) and 32 patients with unipolar depression were included for analyses. Thirty-five participants served as the control group. The study of speech understanding was carried out using the Polish Sentence Matrix Test, allowing for the determination of the speech reception threshold (SRT). The test was performed in the clinical groups both during an acute episode and remission; during remission, patients underwent audiometric evaluation. RESULTS: Compared with control subjects, patients with mood disorders had worse speech understanding (higher SRT), regardless of the episode or remission. A manic episode in the course of bipolar disorder was not associated with worse speech understanding compared with remission of mania. However, an episode of depression in the course of both bipolar disorder and unipolar depression was associated with worse speech understanding compared with remission of depression. In bipolar depression, this correlated with age, duration of the disorder, number of episodes, and number of hospitalizations, as well as in remission with age and duration of illness. In unipolar depression, poor speech understanding was more severe in individuals with hearing impairment. CONCLUSIONS: These findings revealed that patients with mood disorders had impaired speech understanding, even while in remission, and manic episodes in the course of bipolar disorder were not associated with impaired speech understanding compared with mania remission.

Gender, age at onset, and duration of being ill as predictors for the long-term course and outcome of schizophrenia: an international multicenter study.

BACKGROUND: The aim of the current study was to explore the effect of gender, age at onset, and duration on the long-term course of schizophrenia. METHODS: Twenty-nine centers from 25 countries representing all continents participated in the study that included 2358 patients aged 37.21 ± 11.87 years with a DSM-IV or DSM-5 diagnosis of schizophrenia; the Positive and Negative Syndrome Scale as well as relevant clinicodemographic data were gathered. Analysis of variance and analysis of covariance were used, and the methodology corrected for the presence of potentially confounding effects. RESULTS: There was a 3-year later age at onset for females (P < .001) and lower rates of negative symptoms (P < .01) and higher depression/anxiety measures (P < .05) at some stages. The age at onset manifested a distribution with a single peak for both genders with a tendency of patients with younger onset having slower advancement through illness stages (P = .001). No significant effects were found concerning duration of illness. DISCUSSION: Our results confirmed a later onset and a possibly more benign course and outcome in females. Age at onset manifested a single peak in both genders, and surprisingly, earlier onset was related to a slower progression of the illness. No effect of duration has been detected. These results are partially in accord with the literature, but they also differ as a consequence of the different starting point of our methodology (a novel staging model), which in our opinion precluded the impact of confounding effects. Future research should focus on the therapeutic policy and implications of these results in more representative samples.

Antiviral, immunomodulatory, and neuroprotective effect of lithium.

Currently, in psychiatry, lithium is a drug of choice as a mood stabilizer in the maintenance treatment of bipolar disorder for the prevention of manic and depressive recurrences. The second most important psychiatric use of lithium is probably increasing the efficacy of antidepressants in treatment-resistant depression. In addition to its mood-stabilizing properties, lithium exerts antisuicidal, antiviral, immunomodulatory, and neuroprotective effects. The goal of the review is to describe the experimental and clinical studies on the last three properties of lithium. Antiviral effects of lithium pertain mostly to DNA viruses, especially herpes viruses. The therapeutic effects of lithium in systemic and topical administration on labial and genital herpes were demonstrated in clinical studies. There is also some evidence, mostly in experimental studies, that lithium possesses antiviral activity against RNA viruses, including coronaviruses. The immunomodulatory effect of lithium can mitigate "low-grade inflammatory" conditions in bipolar illness. The neuroprotective properties of lithium make this ion a plausible candidate for the prevention and treatment of neurodegenerative disorders. A favorable effect of lithium was shown in experimental models of neurodegenerative disorders. On the clinical level, some preventive action against dementia and moderately therapeutic activity in Alzheimer's disease, and mild cognitive impairment were observed. Despite promising results of lithium obtained in animal models of Huntington's disease and amyotrophic lateral sclerosis, they have not been confirmed in clinical studies. A suggestion for common mechanisms of antiviral, immunomodulatory, and neuroprotective effects of lithium is advanced.

Modeling psychological function in patients with schizophrenia with the PANSS: an international multi-center study.

BACKGROUND: The aim of the current study was to explore the changing interrelationships among clinical variables through the stages of schizophrenia in order to assemble a comprehensive and meaningful disease model. METHODS: Twenty-nine centers from 25 countries participated and included 2358 patients aged 37.21 ± 11.87 years with schizophrenia. Multiple linear regression analysis and visual inspection of plots were performed. RESULTS: The results suggest that with progression stages, there are changing correlations among Positive and Negative Syndrome Scale factors at each stage and each factor correlates with all the others in that particular stage, in which this factor is dominant. This internal structure further supports the validity of an already proposed four stages model, with positive symptoms dominating the first stage, excitement/hostility the second, depression the third, and neurocognitive decline the last stage. CONCLUSIONS: The current study investigated the mental organization and functioning in patients with schizophrenia in relation to different stages of illness progression. It revealed two distinct "cores" of schizophrenia, the "Positive" and the "Negative," while neurocognitive decline escalates during the later stages. Future research should focus on the therapeutic implications of such a model. Stopping the progress of the illness could demand to stop the succession of stages. This could be achieved not only by both halting the triggering effect of positive and negative symptoms, but also by stopping the sensitization effect on the neural pathways responsible for the development of hostility, excitement, anxiety, and depression as well as the deleterious effect on neural networks responsible for neurocognition.

Expression Biomarkers of Pharmacological Treatment Outcomes in Women with Unipolar and Bipolar Depression.

INTRODUCTION: This study aimed to find the expression biomarkers of pharmacological treatment response in a naturalistic hospital setting. Through gene expression profiling, we were able to find differentially-expressed genes (DEGs) in unipolar (UD) and bipolar (BD) depressed women. METHODS: We performed gene expression profiling in hospitalized women with unipolar (n=24) and bipolar depression (n=32) who achieved clinical improvement after pharmacological treatment (without any restriction). To identify DEGs in peripheral blood mononuclear cells (PBMCs), we used the SurePrint G3 Microarray and GeneSpring software. RESULTS: After pharmacological treatment, UD and BD varied in the number of regulated genes and ontological pathways. Also, the pathways of neurogenesis and synaptic transmission were significantly up-regulated. Our research focused on DEGs with a minimum fold change (FC) of more than 2. For both types of depression, 2 up-regulated genes, OPRM1 and CELF4 (p=0.013), were significantly associated with treatment response (defined as a 50% reduction on the Hamilton Depression Rating Scale [HDRS]). We also uncovered the SHANK3 (p=0.001) gene that is unique for UD and found that the RASGRF1 (p=0.010) gene may be a potential specific biomarker of treatment response for BD. CONCLUSION: Based on transcriptomic profiling, we identified potential expression biomarkers of treatment outcomes for UD and BD. We also proved that the Ras-GEF pathway associated with long-term memory, female stress response, and treatment response modulation in animal studies impacts treatment efficacy in patients with BD. Further studies focused on the outlined genes may help provide predictive markers of treatment outcomes in UD and BD.

Lithium treatment in the era of personalized medicine.

In 1949, an Australian psychiatrist, John Cade, reported on the antimanic efficacy of lithium carbonate, which is regarded as an introduction of lithium into contemporary psychiatry. Since the 1960s, lithium has been a precursor of mood stabilizers and has become first-choice drug for the prevention of affective episodes in mood disorders. For nearly four decades, lithium has also been used for the augmentation of antidepressant drugs in treatment-resistant depression. The knowledge of clinical and biological factors connected with the capability of long-term lithium treatment to prevent manic and depressive recurrences makes an important element of the personalized medicine of mood disorders. Excellent prophylactic lithium responders can be characterized by distinct mood episodes, with full remissions between them, the absence of other psychiatric morbidity, and the family history of bipolar illness. In recent years, many other clinical and biological factors connected with such a response have been identified, helping to select the best candidates for lithium prophylaxis. The antisuicidal effect of lithium during its long-term administration has been demonstrated and should also be taken into account as the element of personalized medicine for the pharmacological prophylaxis of patients with mood disorders. Several studies pertaining to personalized medicine were also dedicated to lithium treatment of acute mood episodes. Lithium still has a value in the treatment of mania and bipolar depression. However, it seems that the more important indication would be the augmentation of antidepressant drugs in treatment-resistant depression. The factors connected with the efficacy of lithium in these conditions are reviewed.

Transcriptome Changes in Three Brain Regions during Chronic Lithium Administration in the Rat Models of Mania and Depression.

Lithium has been the most important mood stabilizer used for the treatment of bipolar disorder and prophylaxis of manic and depressive episodes. Despite long use in clinical practice, the exact molecular mechanisms of lithium are still not well identified. Previous experimental studies produced inconsistent results due to different duration of lithium treatment and using animals without manic-like or depressive-like symptoms. Therefore, we aimed to analyze the gene expression profile in three brain regions (amygdala, frontal cortex and hippocampus) in the rat model of mania and depression during chronic lithium administration (2 and 4 weeks). Behavioral changes were verified by the forced swim test, open field test and elevated maze test. After the experiment, nucleic acid was extracted from the frontal cortex, hippocampus and amygdala. Gene expression profile was done using SurePrint G3 Rat Gene Expression whole transcriptome microarrays. Data were analyzed using Gene Spring 14.9 software. We found that chronic lithium treatment significantly influenced gene expression profile in both mania and depression models. In manic rats, chronic lithium treatment significantly influenced the expression of the genes enriched in olfactory and taste transduction pathway and long non-coding RNAs in all three brain regions. We report here for the first time that genes regulating olfactory and taste receptor pathways and long non-coding RNAs may be targeted by chronic lithium treatment in the animal model of mania.

Decreased leucocyte telomere length in male patients with chronic bipolar disorder: lack of effect of long-term lithium treatment.

OBJECTIVES: Bipolar disorder (BD) may be connected with accelerated aging, the marker of this can be shorter telomere length (TL). Some data suggest that lithium may exert a protective effect against telomere shortening. The study aimed to compare the TL between patients with BD and control subjects. The effect of long-term lithium treatment was also assessed. METHODS: The study group comprised 41 patients with BD, including 29 patients treated longitudinally with lithium (mean 16.5 years) and 20 healthy people. TL was assessed by the quantitative polymerase chain reaction (qPCR). RESULTS: In the control group, the TL was significantly longer in males than in females. Male bipolar patients had significantly shorter TL compared with the control male group. In bipolar patients, there was no correlation between TL and duration of treatment. The TL was negatively correlated with age in male bipolar patients. CONCLUSIONS: The study did not confirm the lithium effect on TL in bipolar patients. TL showed gender differences, being shorter in BD males, compared to control males, and longer in healthy males, compared to control females.

Negative symptoms in schizophrenia, assessed by the brief negative symptom scale, self-evaluation of negative symptom scale, and social cognition: a gender effect.

OBJECTIVE: Negative symptoms of schizophrenia can be related to social cognition. The aim was to measure a relationship between the results on the new scales for the assessment of negative symptoms such as the Brief Negative Symptom Scale (BNSS) and Self-evaluation of Negative Symptoms (SNS), and the measures of social cognition. METHODS: The study included 80 patients (40 men, 40 women) with schizophrenia, aged 19-63 (mean 38 years), during the improvement period. They were assessed using the BNSS, SNS, Personal and Social Performance (PSP) scales, and the tests for social cognition such as the Facial Emotion Identification Test, Reading the Mind in Eyes Test, Strange Stories and Faux Pas Test. RESULTS: Male patients obtained higher scores than females when assessed by the BNSS. No gender differences were observed for the SNS scale. Female patients scored better in the PSP and both parts of the Faux Pas test and obtained a significant correlation between the results of the SNS scale, BNSS, PSP, and the affective part of the Faux-Pas test what was not the case in males. CONCLUSIONS: Gender differences were found in the assessment of negative symptoms by a clinical scale and the relationship between negative symptoms and social cognition.KEY POINTSFemale patients scored better in the BNSS, PSP and both parts of the Faux-Pas testGender differences were present in the assessment of negative symptoms by clinical (BNSS) but not the self-assessment (SNS) scale.Female patients obtained a significant correlation between the results of the SNS scale, BNSS, PSP, and the affective part of the Faux-Pas test what was not the case in male subjects.

Attitudes Towards ECT: A Survey of Polish Mental Health Professionals.

BACKGROUND: Although the efficacy of electroconvulsive therapy (ECT) has been well established, the utilization rate of ECT has decreased in Poland in recent years. One of the main reasons could be the negative attitude towards ECT in the community and by mental health professionals. The aim of this study was to assess the knowledge about and attitudes toward ECT in Polish mental health professionals including psychiatrists and non-physicians: nurses, psychologists, social workers. SUBJECTS AND METHODS: Psychiatrists and other mental health professionals in two large Polish hospitals were approached to participate in the survey by completing a 28-item questionnaire. The specific hospitals have been selected due to the fact that they were located in the same province of Poland (Mazowsze), had similar catchment area and profile, provided similar mental health services with only one exception; one offered ECT while the other did not. Of the 185 questionnaires that had been distributed, 165 were completed yielding a response rate of 89.19%. The study population consists of 85 psychiatrists and trainees and 80 non-physicians. RESULTS: Psychiatrists did not differ from other mental health professionals with respect to the knowledge and attitudes toward ECT. However, there were significant differences in the attitude (9.1±3.8 vs 7.1±3.3; p<0.001) and knowledge (5.9±3.8 vs 2.8±4.1; p<0.001) scores between those professionals, who have ever worked in a psychiatric ward where they could observe ECT sessions and those who have not had such an opportunity. CONCLUSIONS: Frequent witnessing of ECT sessions seems to be the most effective educational intervention to change negative attitudes towards ECT.

Lithium - past, present, future.

OBJECTIVES: A narrative review of past, present, and future of lithium use in psychiatry. METHODS: The most important references on the topic were reviewed with special emphasis on the author's works. RESULTS: The history of medical and psychiatric use of lithium dates back to more than one and a half-century ago. However, modern psychiatric history began with the publication of John Cade, in 1949, showing a therapeutic effect of lithium in mania. Currently, lithium is a drug of choice as a mood-stabilizer for the maintenance treatment of the bipolar disorder. The second most important use of lithium is probably augmentation of antidepressants in treatment-resistant depression. In addition to its mood-stabilizing properties, lithium exerts anti-suicidal, immunomodulatory, and neuroprotective action. The drug may protect against dementia and some promising effects of lithium in neurodegenerative disorders have been observed. CONCLUSION: Given the clinical and biological properties of lithium, this drug is presently greatly underutilized in mood disorders. Therefore, the efforts should be undertaken for challenging a skepticism about the use of lithium and optimizing its long-term administration. In such a way, more patients with mood disorders can become the beneficiaries of lithium's therapeutic action. KEY POINTS Lithium is a drug of choice as a mood-stabiliser for the maintenance treatment of bipolar disorder. Augmentation of antidepressants by lithium is one of the best strategies in treatment-resistant depression. Lithium exerts anti-suicidal, immunomodulatory, and neuroprotective action and may protect against dementia. Despite the evidence for the efficacy and added favourable properties, lithium is greatly underutilised in mood disorders. Challenging a scepticism about the use of lithium and optimising its long-term administration can make more patients with mood disorders the beneficiaries of lithium's therapeutic action.

Staging of Schizophrenia With the Use of PANSS: An International Multi-Center Study.

INTRODUCTION: A specific clinically relevant staging model for schizophrenia has not yet been developed. The aim of the current study was to evaluate the factor structure of the PANSS and develop such a staging method. METHODS: Twenty-nine centers from 25 countries contributed 2358 patients aged 37.21 ± 11.87 years with schizophrenia. Analysis of covariance, Exploratory Factor Analysis, Discriminant Function Analysis, and inspection of resultant plots were performed. RESULTS: Exploratory Factor Analysis returned 5 factors explaining 59% of the variance (positive, negative, excitement/hostility, depression/anxiety, and neurocognition). The staging model included 4 main stages with substages that were predominantly characterized by a single domain of symptoms (stage 1: positive; stages 2a and 2b: excitement/hostility; stage 3a and 3b: depression/anxiety; stage 4a and 4b: neurocognition). There were no differences between sexes. The Discriminant Function Analysis developed an algorithm that correctly classified >85% of patients. DISCUSSION: This study elaborates a 5-factor solution and a clinical staging method for patients with schizophrenia. It is the largest study to address these issues among patients who are more likely to remain affiliated with mental health services for prolonged periods of time.

Glutamate-Related Antibodies and Peripheral Insulin-Like Growth Factor in Bipolar Disorder and Lithium Prophylaxis.

AIMS: The aim of this study was to evaluate serum levels of the antineuronal antibodies anti-N-methyl-D-aspartate receptor (NMDAR) and anti-glutamic acid decarboxylase (GAD), and insulin-like growth factor 1 (IGF-1), in patients with bipolar disorder (BD), during manic and depressive episodes and in remission compared to euthymic patients receiving long-term lithium therapy. METHODS: Serum levels of anti-NMDAR and anti-GAD 450/620 antibodies, as well as IGF-1, were measured using the ELISA method in 19 manic and 17 depressed patients both in an acute episode and in remission after the episode. All of the subjects were under pharmacological treatment. The control group included 18 euthymic BD patients receiving lithium for 9-44 years (mean 22 ± 11) in whom a single measurement was performed. RESULTS: Serum levels of anti-NMDAR antibodies were higher in acute manic episodes than in lithium-treated patients. Serum levels of anti-GAD 450/620 antibodies were higher in acute manic and depressive episodes compared to remission after the respective episode. Their values in both acute manic and depressive episodes were higher than those in lithium-treated patients. Serum levels of IGF-1 were higher in acute manic episodes and in remission after mania than in lithium-treated patients. CONCLUSION: Higher levels of anti-NMDAR and anti-GAD antibodies during episodes may point to an abnormality in the glutamatergic system in BD. Increased levels of IGF-1 during an acute manic episode and in remission after mania may constitute a compensatory mechanism against excitotoxicity. Lower levels of anti-NMDAR, anti-GAD antibodies, and IGF-1 during long-term lithium treatment may reflect normalization of this processes, contributing to mood stabilization.

120th Anniversary of the Kraepelinian Dichotomy of Psychiatric Disorders.

PURPOSE OF REVIEW: Emil Kraepelin, in 1899, proposed a dichotomy of psychiatric disorders into "dementia praecox," further called schizophrenia, and "manisch-depressives Irresein," now conceptualized as a bipolar disorder. The purpose of the review is to show both similarities and differences between disorders involved in this dichotomy, speaking for and against the idea. RECENT FINDINGS: On the molecular genetic side, there are data for both a genetic overlap and genetic differences between these two illnesses. Among pharmacological treatment, lithium, valproates, and carbamazepine present evidence for Kraepelinian dichotomy while atypical antipsychotics speak against this. The recent results for similarities and differences in the immune system, cognitive functions, and neurodevelopmental mechanisms have also been presented and discussed. As of 2019, the Kraepelinian dichotomy has been still partly valid although the results of recent clinical, neurobiological, and pharmacological studies provided a large number of data for an intermediate space between schizophrenia and bipolar disorder.

Thyroid structure and function in long-term lithium-treated and lithium-naïve bipolar patients.

OBJECTIVE: The aim of the study was to compare the structure and function of the thyroid in patients with bipolar disorder (BD) receiving long-term lithium treatment, with BD patients never receiving lithium. METHODS: Ninety-eight patients (68 female and 30 male), aged 62 ± 13 years, receiving lithium for 3-47 years (mean 19 ± 10 years), and 39 patients (27 female and 12 male), aged 57 ± 10 years, receiving other mood-stabilizing drugs but never treated with lithium, were included. The thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), and free thyroxine (fT4) were estimated, and the ultrasonographic study of the thyroid gland was performed. RESULTS: Compared with patients not receiving lithium, lithium-treated patients had significantly higher concentrations of TSH and fT4 and the lower concentration of fT3. However, the percentage of hypothyroidism was not different in both groups. Lithium-treated patients also had significantly higher thyroid volume, the higher number of focal changes >1 cm, and more frequent goiter. The structural changes were not related to the hormones' concentrations. CONCLUSIONS: The results show a significant association between long-term lithium treatment and the increase of TSH and fT4, the decrease of fT3, higher thyroid volume, and more frequent goiter and nodular goiter. The effect of lithium on thyroid structure was not associated with its effect on thyroid hormones.

Augmentation of Pharmacotherapy by Sleep Deprivation with Sleep Phase Advance in Treatment-Resistant Depression.

INTRODUCTION: The aim was to assess the efficacy of total sleep deprivation (TSD) with sleep phase advance (SPA) in treatment-resistant depression (TRD) and associated biochemical factors. METHODS: We studied nine males and 12 females, aged 49±14 years, with treatment-resistant unipolar or bipolar depression, receiving antidepressant and mood-stabilizing drugs. The four-day schedule included single TSD and three consecutive nights with SPA. Biochemical markers were measured on the day before and on 1st, 7th and 14th day after the TSD. RESULTS: Ten subjects met criteria for response, defined as a reduction of ≥50% in the Hamilton Depression Rating Scale, on the 14th day. Concentrations of cortisol at baseline were lower in responders, and they decreased during therapy in both groups. In responders, there was an increase of interleukin-10 (IL-10) and IL-1ß on the 14th day. DISCUSSION: Our preliminary study demonstrated the efficacy of pharmacotherapy augmentation by TSD and SPA in half of the patients with TRD. The main biochemical factors related to clinical response included status of cortisol and increase in IL-10 and IL-1ß levels.

No Connection between Long-Term Lithium Treatment and Antithyroid Antibodies.

INTRODUCTION: The studies on the effect of lithium treatment on antithyroid antibodies showed either a higher concentration of these antibodies in patients receiving lithium compared to those lithium-naive or no difference between these groups. In lithium-treated bipolar patients, some researchers pointed to an association between antithyroid antibodies and other features of thyroid dysfunction such as hypothyroidism and decrease of glomerular filtration rate. METHODS: We compared antithyroid antibodies in 98 patients (30 male, 68 female) with bipolar disorder, aged 62±13 years, who received lithium for 19±10 years to 39 patients (12 male, 27 female), aged 57±10 years, who were never treated with lithium. The antibodies against thyroid peroxidase (TPOAb), against thyroglobulin (TGAb), and thyroid-stimulating hormone (TSH) receptors (TSHRAb) were estimated. RESULTS: No difference in the percentages of antibodies occurrence was found between groups, although the concentrations of TGAb were higher in patients receiving lithium. In lithium-treated patients, the presence of TPOAb was associated with lower concentrations of free triiodothyronine and the presence of TGAb, with higher concentrations of TSH. In females, the levels of TGAb were associated with lower thyroid volume. The concentrations of TPOAb correlated positively with the duration of lithium therapy in males, and those of TPOAb and TGAb negatively, with such duration, in female patients. CONCLUSION: The results obtained showed no significant connection between long-term lithium treatment and antithyroid antibodies. In bipolar patients receiving lithium longitudinally, antithyroid antibodies can be associated with some indexes of thyroid function. However, they behave differently in male and female patients.