Catatonia Due to Lithium Neurotoxicity: A Case Report. / Lityum Nörotoksisitesine Ikincil Gelisen Katatoni Vakasi: Bir Olgu Sunumu.

Lithium may cause toxicity as it has a narrow therapeutic range. Lithium intoxication may manifest in the form of acute, acute on chronic and chronic intoxication. Neurotoxicity is a common component of chronic lithium intoxication and the symptoms include tremor, ataxia, dysarthria, extrapyramidal symptoms, hyperreflexia, seizures and status epilepticus. Although rare, catatonia could as a manifestation of lithium neurotoxicity. In this report, we present a patient with bipolar disorder presenting with catatonic symptoms secondary to lithium intoxication. We will discuss the risk factors, differential diagnosis and the treatment of catatonic symptoms. Lithium neurotoxicity may present with various clinical symptoms including catatonia, and differential diagnosis should be made well in such cases. If lithium neurotoxicity is suspected, rapid and appropriate intervention is required to prevent permanent neurological damage. Keywords: Lithium, Neurotoxicity, Catatonia.

12 Psychiatrists who Shaped Psychiatry in Turkey in the Republic's First Century. / Cumhuriyetin 100 Yilinda Türkiye'de Psikiyatriyi Sekillendiren 12 Psikiyatr.

Who are the influential figures that molded Turkish Psychiatry into what it is today? This review introduces 12 psychiatrists who shaped psychiatry in Turkey during the first century of the Republic. The article presents Rasit Tahsin, the first neuropsychiatrist who establish an academic psychiatry department in Turkey; Mazhar Osman, who had so much influence that his name became a phrase to describe the mentally ill, and still lives on with the institutions he built; Ihsan Sukru, the founder of neuropathology in Turkey, a historical figure in viral encephalitis research; Fahrettin Kerim Gokay, famous for his political career and his fight against alcohol and tobacco; Rasim Adasal, a Cretian who is a cornerstone in Ankara psychiatry and a well-known figure in Turkish society life; Abdulkadir Ozbek, who introduced psychodrama to Anatolia-his 'earth'; Leyla Zileli, who disseminated psychoanalysis from Ankara to Turkey; Orhan Ozturk, a founding figure for the Journal, the Association, and Hacettepe; Ayhan Songar, a prominent figure in society and also in state bureaucracy; Ozcan Koknel, the amiable face of psychiatry in society and a respected voice; Oguz Arkonaç, a vigorous advocate for the establishment of contemporary psychiatry with DSM III in Bakirköy and then in Turkey; and Gunsel Koptagel-Ilal, who progressed the work in the psychosomatics as one of Turkey's first female psychiatry academics. As with any list, we acknowledge that absolute consensus is not possible; we are preparing a more extensive selection to be published as a book next year. We present our selection to your liking, hoping that one or more of our colleagues reading this article will be included in the selection for the next century, reflecting our collective conscious creation of psychiatry in Turkey. Keywords: Neuropsychiatry, History, Medicine, Turkey, Psychoanalysis, Psychosomatics.

Minimal Self Disorders in Schizophrenia. / Sizofrenide Yalin Kendilik Bozukluklari.

In recent years we have witnessed a rebirth of interest in the field of subjectivity and its disorders, particularly the severity and quality of non-psychotic abnormal subjective experience. Contemporary research on abnormal subjective experiences in schizophrenia has used several different theoretical frameworks. The most common of these is the phenomenological approach. A prominent example of the phenomenological approach is the minimal self disorder model. In this article, we will discuss, prominent theories on the concept of 'self ', historical background of the minimal self disorder model in schizophrenia and the current approach to this model. According to this model, self disorders have been hypothesized to be an underlying and trait-like core feature of schizophrenia. The model suggests that this minimal self is disturbed in three ways in people with schizophrenia: hyperreflexivity, diminished self-affection (diminished self-presence) and disturbed grip or hold on the cognitive-perceptual world. Hyperreflexivity is defined as the excessive attention to processes that would ordinarily be implicitly experienced. Diminished self-affection (diminished self-presence) refers to an experience of a loss of self-agency. Disturbed grip or hold on the cognitive-perceptual world refers to the disturbances of spatio-temporal structuring of the experiential field. These three aspects are intimately interlinked, and should be understood more as the components of a single entity. Finally, clinical symptoms that may indicate minimal self disorder and the abnormal self experiences of two patients with a diagnosis of schizophrenia are discussed. Keywords: Schizophrenia, phenomenology, self-disorders, hyperreflexivity, diminished self-affection.

[Relationship Between Alcohol Dependence and Neuropeptide Y (NPY) Gene Promoter Polymorphisms in A Turkish Sample]. / Türkiye Örnekleminde Nöropeptit Y Geni (NPY) Promotor Polimorfizmleri ve Alkol Bagimliligi Arasindaki Iliski.

OBJECTIVE: Neuropeptide Y (NPY) is a protein widely expressed in the central nervous system and involved in diverse physiological processes, such as emotional regulation, nutritional behavior, and stress. In some populations, studies on alcohol dependence (AD) and the NPY gene have found that NPY variations increase alcohol consumption and thus may potentially be associated with AD. In this study, we investigated the relationship between NPY gene promoter polymorphisms and phenotypes related to alcohol use. METHOD: A total of 417 male participants comprising 252 individuals with AD and 165 healthy individuals were included in this study and phenotypic data were collected. Polymerase chain reaction-restriction fragment length polymorphism (PCR/RFLP) and DNA sequencing METHODS were used for genotyping the rs16147 and rs17149106 polymorphisms in the promoter region of the NPY gene. The data of 384 participants were analysed to evaluate the possible relationship between genotypes and the diagnosis of AD, family history of AD, the severity of AD using the Michigan Alcoholism Screening Test (MAST), the age of onset of problematic alcohol use, the average amount of alcohol consumed per day for the last six months and the lifetime maximum alcohol consumption in one day. RESULTS: A significant difference was found between the AD and control groups concerning rs16147 polymorphism genotype distribution (p=0.025). No association with polymorphisms and alcohol-related phenotypes were demonstrated in the AD group. CONCLUSION: To our knowledge, this study shows for the first time in the literature that alcohol dependence is associated with NPY rs16147 polymorphism in the Turkish population.

[Effects of Nitric Oxide Synthase-1 Exon 1f-VNTR Gene Polymorphism on the Clinical Symptoms of Alcohol Dependence,Impulsivity and Comorbid Attention Deficit Hyperactivity Disorder]. / Alkol Bagimlilarinda Nitrik Oksit Sentaz-1 Ekzon 1f-VNTR Gen Polimorfizmi’nin Bagimlilik ile Iliskili Klinik Özellikler, Dürtüsellik ve Eslik Eden Dikkat Eksikligi Hiperaktivite Belirtileri Üzerine Etkisi.

OBJECTIVE: We planned to compare individuals with alcohol dependence (AD) and healthy controls on the frequency of NOS1 exon 1f-VNTR gene polymorphism and to investigate the effects of this polymorphism on the clinical symptoms of alcohol dependence, impulsiveness and comorbid attention deficit hyperactivity disorder (ADHD) symptoms. METHOD: A total of 282 participants consisting of 153 patients and 129 age and gender matched healthy individuals were inluded in the study. All participants were evaluated with Structured Clinical Interview for DSM-IV Axis 1 disorders (SCID-I) and Michigan Alcohol Screening Test (MAST), Barratt Impulsiveness Scale (BIS-11), UPPS Impulsive Behavior Scale, Adult Attention Deficit and Hyperactivity Diagnosis Scale (ADHDS), Family History Research Diagnostic Criteria (FHDRC). The QF-PCR fragment protocols were used for genetic analyses. Allele fragments of ≤176 bp and >176 bp sizes were separated and 3 different genotypes were determined as the SS, SL and LL. Associations of these genotypes with symptoms of AD severity, impulsiveness and comorbid ADHD were investigated. RESULTS: The AD and control groups did not differ significantly on the basis of NOS1 exon 1f-VNTR gene polymorphism. Also, significant correlations between this polymorphism and symptoms of AD severity, impulsiveness and ADHD were not determined. CONCLUSION: Results of our study do not indicatea significant association between the NOS1 exon 1f-VNTR genotypes and AD, subgroups of AD, impulsiveness or comorbid ADHD semptoms.

Alteration of the affective modulation of the startle reflex during antidepressant treatment.

Whereas the amplitude of the startle reflex varies with stimulus valence in the normal population, a lack of this affective modulation has been reported in patients with major depressive disorder. The present study sought to clarify blunted startle modulation as a feature of depression by comparing 16 patients diagnosed with major depression prior to and after 2 weeks of SSRI treatment, and 16 healthy controls. The affect-modulated startle reflex paradigm and the Self-Assessment Manikin were used to probe affective reactivity. In addition, a preliminary analysis of change in affective reactivity pattern was performed with depressed patients who could be assessed in the eighth week of treatment (n = 13). The control group showed a linear trend in response across valence categories, which was stable over sessions. Blunted affective reactivity was observed only in the patients and persisted after 2 weeks of treatment. Nevertheless, a linear trend could be detected in the eighth week of treatment. These findings confirm that the affective reactivity is blunted in depression and provide initial evidence for the lack of change in the early phase of SSRI antidepressant treatment. Nevertheless, in a small group, the emergence of a linear trend in response was evident later with treatment. Large-scale studies are required to assess the relation between the treatment response and the change in affective modulation of the startle reflex, as a potential biomarker.

[µ-Opioid Receptor Gene (OPRM1) Polymorphisms A118G and C17T in Alcohol Dependence: A Turkish Sample]. / Türkiye'de Alkol Bagimliliginda µ-Opioid Reseptör Geni (OPRM1) A118G ve C17T Polimorfizmleri.

OBJECTIVES: Previous investigations on opioid system genetics have identified polymorphisms of the OPRM1 gene expressing µ-opioid receptors to be significantly associated with some features of alcohol dependence (AD). In the present study, we evaluated the relationship between single nucleotide polymorphisms (SNP) in the OPRM1 gene, A118G (rs1799971, Asn40Asp) and C17T (rs1799972, Arg6Val), and AD diagnosis, level of alcohol consumption, and AD severity in a Turkish sample. METHODS: 121 AD patients and 117 healthy male subjects were included in the study. OPRM1 A118G (N40D) and C17T (A6V) polymorphisms were evaluated using PCR - RFLP (polymerase chain reaction - restriction fragment length polymorphism) method. We evaluated the association between the presence of SNPs and AD diagnosis, family history of AD, AD severity evaluated via the Michigan Alcoholism Screening Test (MAST), the daily average and maximum quantity of alcohol consumed. RESULTS: There was no significant difference in OPRM1 A118G genotype frequencies between the AD and control groups. T allele frequency for the OPRM1 C17T SNP was very low (0.006) in the sample population. OPRM1 A118G SNP G118 allele carriers showed significantly higher levels of AD severity as indicated by the MAST. CONCLUSION: The OPRM1 G118 allele was significantly associated with more severe AD in the Turkish population. Similar to other European populations, the frequency of the OPRM1 T17 allele was very low.

Association between ADH1C and ALDH2 polymorphisms and alcoholism in a Turkish sample.

BACKGROUND: Polymorphisms in the genes encoding alcohol metabolizing enzymes are associated with alcohol dependence. AIM: To evaluate the association between the alcohol dehydrogenase 1C (ADH1C) Ile350Val and aldehyde dehydrogenase 2 (ALDH2) Glu504Lys polymorphisms and alcohol dependence in a Turkish sample. METHODS: 235 individuals (115 alcohol-dependent patients and 120 controls) were genotyped for ADH1C and ALDH2 with PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism). Association between the polymorphisms and family history, daily and maximum amount of alcohol consumed was investigated. The associations between alcohol dependence, severity of consumption and family history and the polymorphisms were analyzed by chi-square or Fisher's exact test where necessary. Relationship between genotypes and dependence related features was evaluated using analysis of variance (ANOVA). RESULTS: The -350Val allele for ADH1C (ADH1C*2) was increased in alcohol-dependent patients (P = 0.05). In individuals with a positive family history, the genotype distribution differed significantly (P = 0.031) and more patients carried the Val allele compared with controls (P = 0.025). Genotyping of 162 participants did not reveal the -504Lys allele in ALDH2. CONCLUSIONS: These findings suggest that ADH1C*2 is associated with alcohol dependence in the Turkish population displaying a dominant inheritance model. ADH1C*2 allele may contribute to the variance in heritability of alcohol dependence. The ALDH2 -504Lys/Lys or Glu/Lys genotypes were not present in alcohol-dependent patients, similar to that seen in European populations and in contrast to the findings in the Asian populations.

The effects of antidepressants on the results of skin prick tests used in the diagnosis of allergic diseases.

BACKGROUND: Some drugs may cause false negative results by suppressing the reactivity of the skin prick tests (SPTs). The aim of this survey was to show whether escitalopram, fluoxetine and sertraline had any effect on the reactivity of SPT. METHODS: Twenty-four patients who were admitted to the outpatient clinic of the Psychiatry Department at the Hacettepe University Hospital and planned to be treated by these antidepressants were included in the study between May and October 2008. SPTs with positive control (histamine), negative control and 3 common aeroallergens were performed in the beginning, at the first and fourth weeks. A questionnaire including 26 questions about respiratory symptoms and allergic diseases was filled in face to face by the fellow-in-training. The Visual Analog Scale (VAS) of current respiratory and nasal symptoms was recorded at all 3 visits. RESULTS: There were no statistically significant differences between the 3 mean diameters measured at 3 time points in addition to the mean diameters of the wheals between groups using escitalopram, sertraline and fluoxetine (p > 0.05). There was a statistically significant decrease between the VAS of nasal symptoms at the 3 visits (p < 0.05). CONCLUSIONS: Escitalopram, fluoxetine and sertraline do not seem to affect the reactivity of SPTs. Nasal symptoms might have been decreased due to both the allergic treatment suggested and the end of the pollen season.

Hippocampus, glucocorticoids and neurocognitive functions in patients with first-episode major depressive disorders.

The aim of this study was to determine whether there was any relationship between hippocampal volume, and glucocorticoid regulation, and cognitive dysfunctions in drug-naïve major depressive disorder (MDD) patients during their first episode. Twenty drug-free female MDD patients in their first episode and 15 healthy females as control subjects were included in the study. All subjects underwent 3.0 Tesla (T) magnetic resonance imaging (MRI), comprehensive neuropsychological testing and dexamethasone suppression tests (DST). The volumes of the right and left hippocampus of the patients were found to be significantly smaller than those of the controls. Patients were found to have significantly lower scores on measures of attention, working memory, psychomotor speed, executive functions, and visual and verbal memory fields. The performance of the patients only in the recollection memory and memory of reward-associated rules were positively correlated with hippocampal volumes. The volumes of the left and right hippocampus did not correlate with basal or post-dexamethasone cortisol levels. Our findings indicate that depressed patients have smaller hippocampi even in the earlier phase of their illness. Further research efforts are needed to explain the mechanisms that are responsible for the small hippocampus in depressed patients.

The effect of clozapine on regional cerebral blood flow and brain metabolite ratios in schizophrenia: relationship with treatment response.

The purpose of this study was to investigate the effect of clozapine on regional cerebral blood flow (rCBF) and its relationship with response to treatment. In addition, we aimed to study the influence of clozapine on proton magnetic resonance spectroscopy ((1)H-MRS) findings in the dorsolateral prefrontal cortex (DLPFC) in a subgroup of patients. Psychopathology, neurocognitive functioning, and SPECT imaging of 22 patients were assessed at the baseline and 8 weeks after the initiation of clozapine treatment. In 10 of these patients intermediate-echo (TE: 135 ms) single-voxel (1)H-MRS was also performed at the baseline and after 8 weeks. Clozapine treatment increased the right frontal (superior and medial)/caudate perfusion ratio in the whole group, while it increased bilateral frontal (superior and medial)/caudate perfusion ratios in treatment responders. In addition, percentage changes in left and right frontal (superior and medial)/caudate perfusion ratios compared to the baseline were higher in treatment responders than in non-responders. The improvement in attention was related to the increase in percentage change in the right frontal (superior and medial)/caudate perfusion ratio, while the improvement in verbal fluency was related to the increase in percentage changes in both right and left frontal (superior and medial)/caudate perfusion ratios and to right frontal (superior and medial)/thalamus perfusion. Baseline frontal (superior and medial)/thalamus perfusion could explain 32% of the variability of percentage improvements in psychopathology. (1)H-MRS showed that the baseline PANSS general psychopathology score was inversely correlated with the baseline NAA/Cre ratio. An increased NAA/Cre ratio in DLPFC after 8 weeks of clozapine treatment was also revealed by (1)H-MRS. Our SPECT imaging results suggest the presence of an imbalance in fronto-striato-thalamic circuitry that changes with clozapine, especially in the responders, while (1)H-MRS results indicate a supportive effect of clozapine on neuronal integrity.

Antidepressant effect detected on proton magnetic resonance spectroscopy in drug-naïve female patients with first-episode major depression.

AIM: Recent neuroimaging studies support functional and structural alterations in the dorsolateral prefrontal cortex (DLPFC), particularly on the left side in patients with major depressive disorders (MDD). The aim of the present study was to examine the biochemical characteristics of left DLPFC as measured on proton ((1)H) magnetic resonance spectroscopy (MRS) in patients with drug-naïve first-episode MDD and a healthy control group. A second aim was to assess the effect of antidepressant treatment on the metabolites of DLPFC. METHODS: Short-echo single-voxel (1)H-MRS was done for the left DLPFC in 17 female drug-free MDD patients (mean age +/- SD, 30.9 +/- 6.9 years) and 13 matched control subjects (mean age +/- SD, 29.1 +/- 6.2 years) and was repeated at 8 weeks following antidepressant treatment. RESULTS: Comparison of baseline values indicated that there were no significant differences in any of the metabolite ratios (N-acetyl aspartate/creatine [NAA/Cr], myoinositol [Ino]/Cr, and choline [Cho]/Cr) between patients and controls. Significant differences were detected between pre- and post-treatment Ino/Cr ratios (0.67 +/- 0.13, 0.58 +/- 0.22, P = 0.032, respectively), although there was no difference in NAA/Cr and Cho/Cr ratios. CONCLUSION: Although no significant metabolic alterations exist in female patients with drug-naïve first-episode MDD as evaluated on (1)H-MRS, an increase in Ino/Cr was observed following 8-week antidepressant treatment. These findings give rise to the possibility that non-neuronal cells, particularly glial cells that are probably damaged, play a role in the action of antidepressant treatment.

[The association between disability and residual symptoms in depressive patients: a 3-month follow-up]. / Depresyon Tanisi Alan Hastalarda Kalinti Belirtilerin Yetiyitimi ile Iliskisi: 3 Aylik Izlem Calismasi.

OBJECTIVE: In this 3-month naturalistic follow-up we aimed to investigate depression treatment outcome and the correlation between improvement of depressive symptoms and level of disability. METHOD: The study included 104 patients with depression that presented to the Hacettepe Psychiatry Outpatient Clinic. The course was defined operationally using the Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, and Structured Clinical Interview for DSM-IV Axis I Disorders. The World Health Organization Disability Assessment Schedule (WHO-DAS II) was administered to determine level of disability. Patients received follow-up assessments using the same instruments 3 months after receiving antidepressant treatment. RESULTS: Follow-up assessments showed that improvement in Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scale total scores was statistically significant, and lower anxiety and depression ratings were correlated with lower disability levels. The patients that had severe depression and anxiety at the beginning of the course had residual depressive symptoms. The results showed that severity of depression was a predictor of residual symptoms in our cohort. Psychological anxiety was the most common residual symptom (consistent with other studies) and the patients with a psychological anxiety score > or = 2 had higher disability levels (Z = -3.570, P < 0.05). CONCLUSION: Severity of depression was a predictor of residual symptoms and partial remission after a depressive episode appeared to be strongly associated with disability. These findings highlight the importance of adequate treatment of depression.

The effect of clozapine on neuroimaging findings in schizophrenia.

Functional and structural neuroimaging help us to compare the brains of schizophrenic patients and controls, moreover they let us observe the changes with treatment. Longitudinal studies comparing patients with typical and atypical antipsychotics have been useful in understanding the effects of these antipsychotic medications on brain function. In general, atypical antipsychotics are suggested to have greater normalizing effects on brain function than typical, although the results are controversial. In particular, clozapine appears to act more selectively than typical antipsychotics on the prefrontal region, an area of special relevance in higher cognitive functions and schizophrenia. The study of anatomic and functional brain variables associated with clozapine response in schizophrenia may help to identify patients who are most likely to benefit from clozapine treatment. We investigated the effect of clozapine on regional cerebral blood flow and (1)H MRS findings and studied their relationship with treatment response. Clozapine increased frontal/basal ganglia perfusion ratio in treatment-responders. In addition, NAA/Cre ratio has increased and Cho/Cre has decreased in dorsolateral prefrontal cortex after 8 weeks of clozapine treatment. The results of the study will be discussed in the light of current literature. These findings can contribute to better understanding of mechanism of action of clozapine.