Suggested Biomarkers for Major Depressive Disorder.

Currently, the diagnosis of major depressive disorder (MDD) mainly relies on clinical examination and subjective evaluation of depressive symptoms. There is no non-invasive, quantitative test available today for the diagnosis of MDD. In MDD, exploration of biomarkers will be helpful in diagnosing the disorder as well as in choosing a treatment, and predicting the treatment response. In this article, it is aimed to review the findings of suggested biomarkers such as growth factors, cytokines and other inflammatory markers, oxidative stress markers, endocrine markers, energy balance hormones, genetic and epigenetic features, and neuroimaging in MDD and to evaluate how these findings contribute to the pathophysiology of MDD, the prediction of treatment response, severity of the disorder, and identification of subtypes. Among these, the findings related to the brain-derived neurotrophic factor, the hypothalamo-pituitary-adrenal axis, cytokines, and neuroimaging may be strong candidates for being biomarkers MDD, and may provide critical information in understanding biological etiology of depression. Although the findings are not sufficient yet, we think that the results of epigenetic studies will also provide very important contributions to the biomarker research in MDD. The availability of biomarkers in MDD will be an advancement that will facilitate the diagnosis of the disorder, treatment choices in the early stages, and prediction of the course of the disorder.

[Neurobiology of Alcohol Dependence and Implications on Treatment]. / Alkol Bagimliliginin Nörobiyolojisi ve Tedaviye Yansimalari.

The process of alcohol dependence has been conceptualized as a progress from controlled alcohol intake to compulsive alcohol consumption or a shift from alcohol intake for pleasure to compulsory alcohol seeking behavior. Hereditary and physical factors and the interaction of individuals with their environment, as well as permanent changes in the neurotransmitter and neurohormonal systems in the brain due to alcohol use, play the most important role in the etiology of alcohol dependence. The effects of ethanol on the neurotransmitter, neuropeptide and neuroendocrine systems not only account for its acute physiological and euphoric/reinforcing effects but also seem to be responsible for the development of dependence. While the motivation for alcohol use is mainly positive reinforcement in the earlier phases of alcohol consumption, both positive and negative reinforcements are involved in the process once dependence has developed. This event is caused by neuroadaptive process due to chronic alcohol consumption and also called as "allostasis". It seems that the most important neuroadaptive changes in progression from occasional alcohol intake to dependence are the down-regulation of the dopamine and gamma aminobutyric acid systems, permanent upregulation in the glutamate system and dysregulation in the stress systems (corticotropin-releasing hormone and serotonin) of the brain. In this paper, we will review the adaptive changes caused by chronic alcohol consumption which are important in the development of dependence and address the potential therapeutic contributions of interventions to these changes in alcohol dependence.

Relationship between orexin A and childhood maltreatment in female patients with depression and anxiety.

OBJECTIVE: Childhood maltreatment leads to neuroendocrine changes, which may be associated with an increased vulnerability for psychopathology, such as depression and anxiety in later life. This study aimed to investigate the relationship between childhood maltreatment and orexin A levels in patients with depression and anxiety. The study consisted of 27 female outpatients who presented with depressive and/or anxiety symptoms, and 27 healthy female controls. Childhood trauma history was assessed using the childhood trauma questionnaire (CTQ-28) in patients and controls. Serum levels of orexin and cortisol were measured in all subjects. There were positive correlations between serum orexin levels and CTQ total score and between orexin levels and some CTQ subscale scores, such as physical and emotional neglect, in patients. Orexin levels in patients with a positive history of physical and emotional neglect were higher than those in patients with a negative history of them. In the controls, there was a positive correlation between emotional neglect score and serum orexin level. There were no differences in serum levels of orexin and cortisol between patients and controls. Orexin levels may be associated with childhood maltreatment per se, rather than psychopathology, such as depression or anxiety.

Hippocampal volumes and cognitive functions in adult alcoholic patients with adolescent-onset.

This study investigated hippocampal volumes and cognitive functions in adult alcoholic patients with adolescent- or late-onset alcohol use. Twenty-one male alcohol dependent inpatients and 13 healthy male controls were enrolled in this study. Cranial magnetic resonance imaging to measure hippocampal volumes and neuropsychological tests were performed in week 4 of abstinence in the patients and controls. The patients were divided into two subgroups (adolescent- and late-onset subgroups) according to the onset age of alcohol use. Alcoholic patients in general had significantly smaller right hippocampal volumes than the healthy controls. Patients' immediate memory, attention, acquisition and working memory subtest scores were inferior to those of the controls. The right hippocampus was significantly smaller in adult alcoholic patients with adolescent-onset use compared to the controls and the late-onset group. There was no significant correlation between neuropsychological test scores and hippocampal volumes. Our results suggest that hippocampal volume loss might be a feature of adolescent-onset alcoholic patients rather than of late-onset ones.

[Neurobiology of motherhood]. / Anneligin Nörobiyolojisi.

Motherhood is a physiological status in which certain behavioural patterns are exhibited. Maintenance of the life of the species in mammals is dependent upon the presentation of motherhood services in a certain period that the child is dependent on the mother. Absence of the mother causes some deficiencies in social, behavioural and cognitive abilities, an abnormal development of the stress response system, learning and memory disorders, and later, inadequate motherhood skills of the mature offspring during their own maternity period. Because maternal care is extremely important for the survival of the child and thus, for the species to maintain, nature seems to have provided the development of a healthy mother-child relationship. Therefore, motherhood is programmed by the evolutionary process in the female brain before birth. It is certain that the brain of the mother is very different from the brains of the nulliparous women who are within the same age range, and is very sensitive to her own child's needs. For maternal behaviour to develop in human beings and animals, special neural networks, which are cooperatively developed by genetic, environmental and hormonal factors, are necessary. It also seems likely that non-genetic (epigenetic) transmission responsible for the internalization of maternal behaviours learned from the mother and hormonal exposure of the brain both during the foetal period, throughout the growth, and during the gestation of the woman as well as genetic factors, play an important role in the development of these maternal neural networks and systems. In this paper, which was prepared by obtaining the necessary publications by means of a search for the words related to motherhood in the PubMed search engine, the physical and mental changes that prepare females for motherhood and enable them to tolerate it will be reviewed.

Ultrasonically determined thyroid volume and thyroid functions in lithium-naïve and lithium-treated patients with bipolar disorder: a cross-sectional and longitudinal study.

OBJECTIVE: This study investigated thyroid volume, hormone levels and antibodies in long-term lithium-treated and lithium-naïve bipolar patients, some of whom underwent prospective follow-up evaluations. METHODS: Fourteen lithium-naïve patients, 13 long-term lithium-treated patients diagnosed with bipolar disorder and 12 healthy controls were included. Seven lithium-naïve patients were followed-up during their lithium receiving period (range 6-9 months). Thyroid volume and serum levels of thyroid hormones and antibodies were measured once in the long-term lithium-treated patients and controls, and twice in the lithium-naïve patients, i.e. before and after lithium treatment. RESULTS: Mean thyroid volumes in the lithium-naïve patients were significantly higher than those in the controls. Long-term lithium-treated patients had significantly higher total thyroid volume than the lithium-naïve patients and the controls. Total thyroid volume in the patients after the lithium treatment was significantly higher than that before. Serum free thyroxine (fT4) levels in the long-term lithium-treated patients were lower than those in the lithium-naïve patients and the controls. In the lithium-naïve patients, after lithium treatment, free triiodothyronine (fT3) levels were lower, and thyroid stimulating hormone (TSH) levels were higher compared to those before lithium treatment. CONCLUSIONS: The results suggest that thyroid enlargement and some alterations in thyroid hormones in bipolar patients may present even before lithium treatment and increase further with lithium treatment.

Manic episode associated with mega cisterna magna.

Mega cisterna magna is a part of "Dandy-Walker Complex" and it is characterized by the enlargement of the cisterna magna, morphologically intact vermis and cerebellar hemispheres. We report a case of manic attack in a 23-year-old man with mega cisterna magna. The patient was treated with quetiapine 1,000 mg/day and sodium valproate 1,500 mg/day and the symptoms were ameliorated within 2.5 months. In this case, mega cisterna magna and manic symptoms may be found together coincidentally or any cerebellar dysfunction due to mega cisterna magna may cause or contribute to the appearance of affective symptoms. To our knowledge, this is the first case reporting manic attack with psychotic symptoms associated with mega cisterna magna. This report suggests that any lesion in the cerebellum might contribute to the occurrences of some affective and psychotic symptoms seen in bipolar disorder.

Serum oxytocin levels in patients with depression and the effects of gender and antidepressant treatment.

Abnormalities in the neurohypophyseal system have been reported in depression. This study aimed to investigate serum oxytocin levels in patients with depression and the effects of gender and antidepressant treatment on these levels. Serum oxytocin levels were measured before and after treatment with antidepressant drugs or electroconvulsive therapy (ECT) in 40 inpatients (30 women, 10 men) who met the DSM-IV criteria for major depressive disorder (n=29) or bipolar affective disorder depressive episode (n=11), and in 32 healthy controls (20 women, 12 men). Serum oxytocin levels were decreased both pre-treatment and post-treatment in the patients compared with those in the controls. Serum oxytocin levels were not affected by antidepressant drug treatment or ECT. The female patients had significantly lower oxytocin levels than the control females, whereas no difference was found between the male patients and the male controls. We found no difference in serum levels of oxytocin between the unipolar and bipolar depressive patients. Our result shows reduced oxytocin in depression and a gender difference in oxytocin levels. Furthermore, antidepressant treatments appear to have no effect on serum oxytocin levels.

The effects of galantamine hydrobromide treatment on dehydroepiandrosterone sulfate and cortisol levels in patients with chronic fatigue syndrome.

OBJECTIVE: Mental fatigue, cognitive disorders, and sleep disturbances seen in chronic fatigue syndrome (CFS) may be attributed to cholinergic deficit. A functional deficiency of cholinergic neurotransmission may cause the hypothalamic-pituitary-adrenal axis hypoactivity seen in CFS. Therefore, we investigated the alterations in stress hormones such as cortisol and dehydroepiandrosterone sulfate (DHEAS) in CFS patients before and after 4-week administration of galantamine hydrobromide, a selective acetylcholinesterase inhibitor, and aimed to investigate whether there are any relationships between the probable hormonal changes and cholinergic treatment. METHODS: Basal levels of cortisol and DHEAS were measured in 29 untreated CFS patients who were diagnosed according to Centers for Disease Control (CDC) criteria and in 20 healthy controls. In the patient group, four weeks after 8 mg/d galantamine hydrobromide treatment, cortisol and DHEAS levels were measured again. After the treatment 22 patients who stayed in study were divided into two subgroups as responders and nonresponders according to the reduction in their Newcastle Research Group ME/CFS Score Card (NRG) scores. RESULTS: Important findings of this study are lower pre-and post-treatment cortisol levels and in all CFS patients compared to controls (F=4.129, p=0.049; F=4.803, p=0.035, respectively); higher basal DHEAS values and higher DHEAS/cortisol molar ratios which were normalized following four weeks' treatment with 8 mg/d galantamine hydrobromide in the treatment-respondent group (F=5.382, p=0.029; F=5.722, p=0.025, respectively). CONCLUSION: The findings of the decrease in basal DHEAS levels and DHEAS/cortisol molar ratios normalizing with galantamine treatment may give some support to the cholinergic deficit hypothesis in CFS.

[Acute and chronic effects of electroconvulsive therapy on neuroactive steroids in patients with major depressive disorder]. / Major depresif bozuklugu olan hastalarda elektrokonvulsif tedavinin nöroaktif steroidler üzerine akut ve uzun süreli etkisi.

OBJECTIVE: Baseline serum levels of neuroactive steroids such as dehydroepiandrosterone sulfate (DHEAS), 17-hydroxyprogesterone (17-OHP), testosterone, and cortisol were measured, and the acute and long-term effects of electroconvulsive therapy (ECT) on these hormones and the effect of gender on alterations in steroid hormones were investigated in patients with major depressive disorder (MDD). METHODS: The study included 25 inpatients (11 male, 14 female) diagnosed with MDD that responded to ECT, and 37 healthy controls (17 male, 20 female). Serum levels of cortisol, DHEAS, 17-OHP, and testosterone were measured 2 days before and 10 min after the first ECT, and 3 days after the last ECT in the patients. These measurements were obtained only once in the controls. RESULTS: Basal DHEAS increased, testosterone and 17-OHP decreased, and cortisol levels remained unchanged in MDD patients as compared to the controls. After completion of the therapeutic course of ECT, DHEAS levels in the patients were higher than they were before the treatment. After ECT treatment, cortisol and 17-OHP levels in the patients were lower than those in the controls; however, testosterone levels did not differ between the groups. In the MDD patients, increases in DHEAS and decreases in testosterone were only observed in men, while decreases in 17-OHP were only seen in women. CONCLUSIONS: Alterations were observed in some neuroactive steroids in MDD patients and it appears that ECT affected these hormones. It is not clear whether the observed alterations in neuroactive steroids are associated with the pathophysiology of depression or whether they play a role in the therapeutic effects of ECT.

The effects of electroconvulsive therapy on GABAergic function in major depressive patients.

OBJECTIVES: It has been proposed that major depression is associated with a dysfunction of the gamma-aminobutyric acid (GABA) system. This study was planned to investigate whether there are any alterations in GABAergic activities in major depressive patients and, if there are, whether electroconvulsive therapy (ECT) has any effect on these changes. METHODS: Twenty-five depressed inpatients who responded to a course of ECT and 23 healthy subjects were included in the study. Serum GABA levels were measured 2 days before and 10 minutes after the first ECT and 3 days after the last ECT, and a baclofen challenge test was performed 2 days before the first ECT and 3 days after the last ECT in the patients. The same tests were carried out only once in the control group. RESULTS: Depressive patients had lower serum GABA levels compared with healthy individuals, and ECT caused a significant increase in these levels. The acute effect of the one-ECT procedure was a huge increase in the baseline GABA levels. Although there was no difference in the maximum alteration in growth hormone with baclofen between the patients and controls before the therapeutic ECT course, it became significantly higher in the depressive patients than in the controls after the treatment. CONCLUSIONS: The findings of this study support the GABA deficit hypothesis of major depression because major depressive patients have lower levels of serum GABA that are increased by a completed ECT course. ECT seems to increase brain GABA levels as well as GABAB activity, and these effects may contribute to its mechanism of therapeutic effect.

Hypothalamic-pituitary-adrenal axis activity, dehydroepiandrosterone sulphate and their relationships with aggression in early and late alcohol withdrawal.

The study aims at investigating the relationship between hypothalamic-pituitary-adrenal (HPA) axis alterations and aggression level in alcoholic patients during early and late alcohol withdrawal. Serum levels of basal cortisol and dehydroepiandrosterone sulphate (DHEAS) were measured three times, and cortisol and DHEAS response to dexamethasone twice during the early and late withdrawal periods in alcohol dependent males (n=30) and once in healthy control males (n=20). Abnormal cortisol non-suppression response to dexamethasone in dexamethasone suppression test (DST) was observed in some proportion of the patients in early withdrawal, which normalized in late withdrawal. The study revealed reduced basal DHEAS levels and reduced DHEAS response to dexamethasone in late withdrawal. When the patients were assessed in two separate groups as high- and low-aggressives, in the high-aggression group abnormality in DST was observed during both early and late withdrawal periods, in the low-aggression group it was observed only in early withdrawal. While basal DHEAS levels were low in the high-aggression group only in early withdrawal, it was reduced in the low-aggression group during late withdrawal period. Some alterations of the HPA axis during alcohol withdrawal might be associated not only with alcohol use per se but also with aggressivity tendency of alcoholic patients.

Growth hormone response to the GABA-B agonist baclofen in 3-week abstinent alcoholics.

Gamma-aminobutyric acid (GABA) dysfunction is a known feature of alcoholism. We investigated GABA-B receptor activity in 3-week abstinent alcoholics using the growth hormone (GH) response to baclofen, a GABA-B receptor agonist. The study aimed to investigate the relationship between GABA-B receptor activity and alcohol withdrawal. GH response to baclofen was measured in alcohol-dependent males without depression (n = 22) who were on day 21 of alcohol abstinence and in healthy control male subjects (n = 23). After 20mg baclofen was given orally to the subjects, blood samples for GH assay were obtained every 30 min for the subsequent 150 min. The patients were divided into two subgroups (continuing withdrawal and recovered withdrawal subgroups) according to their withdrawal symptom severity scores on day 21 of alcohol cessation. Baclofen administration significantly altered GH secretion in the controls, but not in the patients. When GH response to baclofen was assessed as DeltaGH, it was lower in the patients with continuing withdrawal symptoms than in the controls and in the recovered withdrawal group. Impaired GH response to baclofen in all patients mainly pertained to the patients whose withdrawal symptoms partly continued. Our results suggest that reduced GABA-B receptor activity might be associated with longer-term alcohol withdrawal symptoms in alcoholic patients.

Thyroid function in early and late alcohol withdrawal: relationship with aggression, family history, and onset age of alcoholism.

AIMS: Thyroid dysfunction is a known finding in alcoholism. Most studies have reported the reduction in peripheral thyroid hormones in acute withdrawal and long-term abstinence periods of alcohol dependence. The aim of the present study was to investigate the alterations of free thyroid hormones in early and late withdrawal and their association with aggression, age of onset, and family history of alcoholism. METHODS: Male inpatients (n = 39; mean age +/- SD: 42.55 +/- 8.02 years) in alcohol withdrawal were compared with healthy men (n = 28; mean age +/- SD: 38.31 +/- 9.26 years). Levels of free thyroxine (fT4), free triiodothyronine, (fT3) and thyrothrophin (TSH) were measured in early (first day) and late (28th day) withdrawal in the patients and only once in the controls. RESULTS: In early withdrawal, levels of thyroid hormones did not differ from those in the controls. In late withdrawal, fT3 and fT4 levels (2.71 +/- 0.56 and 10.80 +/- 1.86 pg/ml) were lower than those of both controls (3.32 +/- 0.41 and 11.95 +/- 1.49 pg/ml, respectively, P < 0.05 in both cases) and patients in early withdrawal (3.18 +/- 0.72 and 12.68 +/- 2.50 pg/ml, respectively, P < 0.05 in both cases). Patients were divided into subgroups according to aggression level, onset age of alcoholism, and family history. While the high-aggression group had lower serum levels of fT3 and fT4 in late withdrawal (2.49 +/- 0.41 and 10.44 +/- 2.15 pg/ml) compared with those of controls (P < 0.05 in both cases), the low-aggression group only had lower serum levels of fT3 in late withdrawal (2.90 +/- 0.62 pg/ml) compared with those of controls (P < 0.05). fT3 and fT4 values in the family history-negative group (2.67 +/- 0.56 and 10.75 +/- 1.88 pg/ml) were lower than those of controls in late withdrawal (P < 0.05 in both cases). Both fT3 and fT4 levels in late withdrawal (2.69 +/- 0.54 and 10.83 +/- 1.96 pg/ml) were decreased in early-onset group compared with those of controls (P < 0.05 in both cases). CONCLUSION: Decreased free thyroid hormone levels may be a result of heavy alcohol consumption or a trait marker of alcoholism, especially in high-aggressive, early-onset and family history-negative patients.

[Neurobiology of alcohol withdrawal inhibitory and excitatory neurotransmitters]. / Alkol Yoksunlugunun Nörobiyolojisi: Baskilayici ve Uyarici Nörotransmiterler.

Alcohol withdrawal is a syndrome that is the result of adaptive changes in the brain secondary to chronic alcohol use and is associated with changes in many neurotransmitter, neuropeptide, and hormonal systems. Long-term exposure to ethanol leads to an imbalance in different excitatory (especially glutamate, a major excitatory amino acid), and inhibitory neurotransmitter (especially GABA, a major inhibitory amino acid) systems. When alcohol consumption is reduced or completely ceases, these imbalances are behaviorally expressed in the form of alcohol withdrawal. Symptoms of alcohol withdrawal are mainly associated with the hypofunction of GABA receptors and enhanced function of NMDA receptors. The imbalance between receptors may be exacerbated by repeated withdrawal. Some of these alterations may last for months following alcohol cessation and cause symptoms of protracted alcohol withdrawal, which may contribute to the continuation of the cycle of alcohol addiction relapses. The search for biological alterations during alcohol withdrawal may not only render some important insights into the pathophysiology of alcohol dependence, but might also identify new targets for the treatment of alcohol withdrawal symptoms and for preventing relapses following withdrawal. Therapists specializing in the treatment of addiction should be cognizant of the underlying biological mechanisms of alcohol withdrawal in order to more adequately understand the physiopathology of substance dependence in general. In this paper, we will review the changes in the inhibitory and excitatory neurotransmitter systems involved in alcohol withdrawal, and we will discuss their roles in the development of alcohol dependence.

Cerebellar syndrome in a patient with pneumonia under lithium treatment: A case report.

We report the case of a 31-year-old man with bipolar disorder who was on a combination therapy of lithium, lamotrigine and escitalopram. Serum lithium level was within therapeutic range. Cerebellar symptoms such as dysarthria, ataxia, and dyskinesia developed in the patient following the pneumonia. Cerebellar syndrome was most likely due to lithium neurotoxicity, which was associated with additional factors such as acute febrile pneumonia, fever and hyponatremia. The reported case suggests that infections may increase the risk of cerebellar toxicity of lithium, even in the therapeutic doses.

[Is there any alteration in bone mineral density in patients with depression?]. / Depresyonlu Hastalarda Kemik Mineral Yogunlugunda Degisiklik Var mi?

OBJECTIVE: Depression is associated with some alterations in behavior and hypothalamic-pituitary-adrenal axis function that may be risk factors for decreased bone mineral density (BMD). There is considerable inconsistency as to whether depressed patients really have decreased BMD or not. Decreased BMD has been reported in patients suffering from major depression in some studies, but not in some others. Moreover, few studies have investigated BMD in male depressed patients. The aim of this study was to investigate BMD in patients with major depression, including male ones. METHOD: BMD was investigated in forty-two inpatients that fully met the DSM-IV criteria for major depressive disorder (21 women, 21 men; mean age+/-SD: 37.57+/-8.70) and compared with that in twenty-three healthy controls (12 women, 11 men; mean age+/-SD: 33.73+/-7.16). The severity of clinical symptomatology was assessed by the Montgomery-Asberg Depression Rating Scale (MADRS). BMDs of lumbar vertebrae (L1-L4) and femur neck were measured using dual energy X-ray absorptiometry. RESULTS: We found no difference in the values of BMDs of lumbar vertebra (L1-L4) and femur neck between depressive patients and controls among women or men. However, BMDs of the males in the control group were higher than those of the healthy females for both regions investigated; this gender difference was not observed in the depressive patients. CONCLUSION: Major depression is not associated with any alteration in BMD either in women or in men.

Effects of antidepressant treatment and of gender on serum leptin levels in patients with major depression.

Leptin is a product of the obese gene and plays an important role in the regulation of body weight and food intake. Weight and appetite are frequently altered in depression. So far, inconsistent results have been reported in terms of leptin levels in depression. Therefore, the authors investigated serum leptin levels in patients with depression and in healthy controls, and whether there was any alteration throughout antidepressant treatment. Female patients showed significantly higher leptin levels than those of the control females both before and after the response to antidepressant treatment, whereas no difference was found between the male patients and the male controls. The improvement from depression with antidepressant treatment caused a further elevation on the leptin levels, in both female and male patients. These findings confirm an increase in leptin levels in depressive patients and presence of a sexual dimorphism. Moreover, clinical response to antidepressant treatment seems to have an additional increasing effect on leptin levels.

Effects of electroconvulsive therapy on the thyrotropin-releasing hormone test in patients with depression.

We investigated the acute and lasting effects of electroconvulsive therapy (ECT) on the thyroid-stimulating hormone (TSH) response to thyrotropin-releasing hormone (TRH) in patients with depression. The TRH stimulation test was conducted (1) under basal conditions, after a first ECT, and at the end of a therapeutic course of 7 ECTs in 20 inpatients with depression; (2) before the initiation of antidepressant therapy and after the therapeutic response in 16 other inpatients with depression who responded to antidepressant drug treatment; and (3) in 20 healthy control subjects. Baseline TSH levels were lower in patients with depression, especially in those with more severe depression who were considered appropriate for ECT. Before the treatment, TSH response to TRH did not differ between the patients with depression and controls; however, more blunted TSH responses to TRH were observed in these patients compared with the controls. TSH response to TRH changed neither with one ECT nor throughout consecutive ECT sessions in patients with depression. Drug treatment also was found to have no impact on this response. These findings suggest that the therapeutic action of ECT in depression is not directly related to its effects on the hypothalamic-pituitary-thyroid axis. However, possible delayed effects of ECT on the HPT axis function should not be overlooked.

A pilot study evaluating anxiety and depressive scores in acne patients treated with isotretinoin.

BACKGROUND: Isotretinoin therapy and its alleged adverse psychiatric effects have received considerable media attention during the past years. The aim of this pilot study was to investigate whether there was any association between isotretinoin therapy and anxiety, depression or suicidal ideation. METHODS: Forty-five patients with severe recalcitrant acne were enrolled in this study. Isotretinoin was administered at a dose of 0.5-1 mg/kg per day in two divided doses with food for 16 weeks. All patients received a complete dermatological examination and the severity levels of their acne were scored according to the Leeds Revised Acne Grading system at baseline (before isotretinoin treatment) and follow-up assessments at weeks 4, 8 and 16 of the treatment. Severity of anxiety and depressive symptoms were assessed with the Clinical Anxiety Scale and Montgomery-Asberg Depression Rating Scale before and upon completion of the 16-week isotretinoin treatment. RESULTS: Twenty-three patients completed the final assessment. There was a statistically significant decrease in anxiety scores. Depression scores also decreased but were not statistically significant. No patient committed or attempted suicide. CONCLUSIONS: This pilot study was unable to detect an association between the use of isotretinoin and an increased risk for anxiety, depression, or suicidal thoughts.