Association Between Polymorphisms of DNA Repair Genes and Risk of Schizophrenia.

AIMS: DNA repair gene polymorphisms have recently been implicated as potential pathogenic contributors of mental disorders. The aims of our study were to investigate the participation of nucleotide and base excision repair mechanisms in schizophrenia and to identify novel candidate DNA repair susceptibility genes. MATERIALS AND METHODS: For these purposes, we genotyped apurinic/apyrimidinic endonuclease 1 (APE1), human 8-oxoguanine DNA N-glycosylase 1 (hOGG1), X-ray repair cross-complementation group 1 (XRCC1), XRCC3, xeroderma pigmentosum group D (XPD), and xeroderma pigmentosum group G (XPG) genes in schizophrenia subjects, their healthy relatives, and unrelated healthy controls. RESULTS: Carriers of XRCC1 glutamine (Gln), XRCC3 threonine (Thr), hOGG1 cysteine (Cys), and XPD lysine (Lys) alleles were significantly more frequent among the cohort of schizophrenia patients than in controls. In contrast, the frequencies of XRCC3 methionine (Met) and XPD Gln allele carriers and hOGG1 serine (Ser)/Ser genotype carriers were higher among controls than in patients, suggesting a possible protective role for these gene variants against schizophrenia. Moreover, healthy relatives had significantly higher frequencies of XRCC3 Thr+ and XPD Lys+ genotypes than unrelated healthy controls. Minor allele frequencies, haplotypes, and overtransmitted alleles of DNA repair genes were also identified. CONCLUSION: Our findings support XRCC1, XRCC3, hOGG1, and XPD as risk genes for schizophrenia and suggest that altered DNA repair functions may be involved in schizophrenia pathophysiology.

Are trauma and dissociation related to treatment resistance in patients with obsessive-compulsive disorder?

OBJECTIVE: Previous research has indicated a relation between obsessive-compulsive disorder (OCD), childhood traumatic experiences and higher levels of dissociation that appears to relate to negative treatment outcome for OCD. The aim of the present study is to investigate whether childhood trauma and dissociation are related to severity of OCD in adulthood. We also intend to examine the association between treatment resistance, dissociation, and each form of trauma. METHODS: Participants included 120 individuals diagnosed with OCD; 58 (48.3 %) of them met the criteria for treatment-resistant OCD (resistant group), whereas the other 62 (51.7 %) were labeled as responder group. The intensity of obsessions and compulsions was evaluated using Yale-brown obsessive-compulsive scale (Y-BOCS). All patients were assessed with the traumatic experiences checklist, dissociative experiences scale, beck depression inventory, and beck anxiety inventory. RESULTS: Controlling for clinical variables, resistant group had significantly higher general OCD severity, anxiety, depression, trauma, and dissociation scores than the responders. Correlation analyses indicated that Y-BOCS scores were significantly related to severity of dissociation, anxiety, depression, and traumatic experiences. In a logistic regression analysis with treatment resistance as a dependent variable, high dissociation levels, long duration of illness, and poor insight emerged as relevant predictors, but gender, levels of anxiety, depression, and traumatic experiences did not. CONCLUSIONS: Our results suggest that dissociation may be a predictor of poorer treatment outcome in patients with OCD; therefore, a better understanding of the mechanisms that underlie this phenomenon may be useful. Future longitudinal studies are warranted to verify if this variable represents predictive factors of treatment non-response.

Clinical characteristics of self-mutilating behavior in Turkish male subjects with antisocial personality disorder: relationship to psychopathy.

AIMS: The aims of this study were to determine the characteristics of self-mutilation (SM) and examine the relationship between SM and psychopathy in male subjects with antisocial personality disorder (APD). METHODS: APD diagnosis was established by the Structured Clinical Interview for DSM-III-R Axis II Disorders. Subjects (N = 116) were assessed using the Psychopathy Checklist-Revised and a semi-structured self-mutilation questionnaire form. RESULTS: In males with APD, the percentages of psychopathy and SM were 48.3% (N =56) and 96.6% (N = 112), respectively. There were positive correlations between severity of psychopathy and severity, number, and frequency of SM. CONCLUSION: Considerably high rates of SM and psychopathy were found in Turkish males with APD. The features of SM were associated with comorbidity of psychopathy. These results showed the importance of exploring the self-injurious behavior and psychopathy when diagnosed with APD.

Plasma orexin A, ghrelin, cholecystokinin, visfatin, leptin and agouti-related protein levels during 6-week olanzapine treatment in first-episode male patients with psychosis.

The objective of the study was to investigate the change of body mass index (BMI), waist circumference, lipid profile, leptin, ghrelin, orexin, visfatin, agouti-related protein, and cholecystokinin levels during 6 weeks of olanzapine treatment in newly diagnosed first-episode drug naive, young adult, nonobese male patients with psychosis. Twenty male participants who were all first-episode drug naive psychotic patients without prominent affective signs and symptoms and 22 healthy male controls of similar age were included. BMI, waist circumference, fasting glucose, and lipid profiles were measured, and Positive and Negative Syndrome Scale and Brief Psychiatric Rating Scale scores were obtained at baseline, during the second and sixth week of treatment, and the aforementioned neuropeptide levels were measured at baseline and during the sixth week of treatment. Treatment was associated with significant increases in BMI, waist circumference, serum triglyceride, and low-density lipoprotein levels. BMI levels increased more than 7% in over 75% of the patients. Leptin increased, and ghrelin and orexin decreased significantly with olanzapine treatment, whereas cholecystokinin, visfatin, and agouti-related protein levels did not change significantly. In conclusion, consistent with previous studies, we found increased BMI, leptin and lipids during olanzapine treatment. Association of neuropeptide level changes with symptom improvement might be mediated by the dopaminergic and serotonergic systems.

Lack of association between DRD3 gene polymorphism and response to clozapine in Turkish schizoprenia patients.

It is hypothesized that molecular components of dopaminergic system, especially the dopamine D3 receptor gene (DRD3), may play a crucial role in the pathophysiology of schizophrenia, because it is abundant in the limbic system of the brain and it binds antipsychotic drugs. Several groups attempted to find an association between a serine-to-glycine polymorphism of the DRD3 gene (Ser9Gly) and schizophrenia; however, the results were inconsistent. In this study, we aimed to investigate the relationship of the Serine/Glycine polymorphism of the DRD3 gene with therapeutic response to clozapine treatment between Turkish schizophrenia patients (N = 92) and healthy controls (N = 100). Genotype groups were comparable in BPRS, SAPS, SANS analysis of response to clozapine. Our results suggest that an association between the Ser/Gly polymorphism of DRD3 gene and response to clozapine in Turkish schizophrenia patients is unlikely to exist.

Self-mutilating behavior in patients with dissociative disorders: the role of innate hypnotic capacity.

BACKGROUND: Despite the fact that the assumption of a relationship between self-mutilation and dissociative disorders (DD) has a long history, there is little empirical evidence to support this premise. The present study examined this relationship and investigated whether this commonality is associated with innate hypnotic capacity. METHODS: Fifty patients diagnosed with DD and 50 control subjects with major depression were assessed by using a self-mutilation questionnaire, Dissociative Experiences Scale, Traumatic Experiences Checklist, and the Eye-Roll Sign for their self-mutilating behaviors, dissociative symptoms, early trauma, and innate hypnotic capacity, respectively. RESULTS: We have found that 82% of the present sample of patients with DD injured themselves. They had higher scores on trauma, dissociation and eye-roll measurements than controls. In addition, DD patients with self-mutilation were more likely to have high scores of trauma, dissociation and eye-roll than those without self-mutilation. Innate hypnotic capacity was a strong predictor of self-mutilating behavior in DD patients. CONCLUSIONS: This study strongly supports the assumption that patients with DD are at high risk for self-mutilating behavior and points to the necessity of routine screening for self-mutilating behavior as well as the hypnotic capacity which may constitute a high risk for self-injury in this patient group.

Effects of diagnostic comorbidity and dimensional symptoms of attention-deficit-hyperactivity disorder in men with antisocial personality disorder.

OBJECTIVE: Although children with attention deficit hyperactivity disorder (ADHD) are at increased risk for later onset of antisocial personality disorder (APD) as adults, the utility of ADHD as either a comorbid diagnosis (ADHD(c)) or dimensional symptoms (ADHD(d)) in predicting behaviour and substance use problems in APD subjects has not been examined. METHOD: A total of 105 adult male offenders with Structured Clinical Interview for Axis II Disorders (SCID-II)-based DSM-III-R APD were studied in terms of: (i) psychopathy scores on the Hare Psychopathy Checklist-Revised (PCL-R); (ii) ADHD(c) diagnostic comorbidity on clinically administered DSM-IV questionnaire; and (iii) ADHD(d) dimensional symptoms by means of Wender Utah Rating Scale (WURS) and Conners Adult ADHD Rating Scale (CAARS) during a 12 month study period (May 2005-May 2006). RESULTS: Sixty five per cent of APD subjects met criteria for ADHD(c) diagnostic comorbidity with significantly increased rates of childhood neglect, parental divorce and suicide attempt, but not of psychopathy. APD subjects with ADHD(d) symptoms were noted to have earlier onset and increased rate of self-injurious behaviour (SIB), suicide attempt, and psychopathy. The psychopathy scores, in turn, were predictive of earlier onset of SIB and behavioural problems. CONCLUSION: Both ADHD(c) diagnostic comorbidity and ADHD(d) symptoms need to be assessed in APD subjects and the dimensional measures may be better in detecting earlier onset SIB, suicide attempt and other behavioural problems.

Nightmare disorder, dream anxiety, and subjective sleep quality in patients with borderline personality disorder.

AIMS: The aims of the present study were to examine the rate of nightmare disorder (ND) and to determine the levels of dream anxiety and subjective sleep quality in patients with borderline personality disorder (BPD). Another aim was to determine whether dream anxiety was associated with childhood trauma, dissociative experiences, and subjective sleep disturbance in BPD patients. Finally, the hypothesis as to whether BPD patients with ND exhibited a more severe clinical profile than those without ND, was also tested. METHODS: A total of 88 borderline patients and 100 age- and sex-matched healthy control subjects were assessed using the Structured Clinical Interview for DSM-III-R Personality Disorders, Structured Clinical Interview for DSM-IV Axis I Disorders, Van Dream Anxiety Scale, Pittsburgh Sleep Quality Index, Dissociative Experiences Scale, and Traumatic Experiences Checklist. Subjects with codiagnoses that could affect sleep were not included. RESULTS: BPD patients suffered a significantly greater rate of nightmares, elevated levels of dream anxiety, and disturbed sleep quality than did controls. In the borderline group, heightened dream anxiety was correlated with higher rates of early traumatic experiences and dissociative symptoms, and impaired sleep quality. Furthermore, borderline patients with ND exhibited greater psychopathology as compared to those without ND in terms of several clinical characteristics. CONCLUSIONS: The present study provides support for a strong association between BPD, distressing nightmares, and subjective sleep quality. Recognition and management of dream and sleep disturbances in BPD patients might lead to improvements in their global clinical picture.

Factitious subcutaneous emphysema of an extremity.

The presence of air in the subcutaneous tissue of an extremity constitutes a fearful finding because of the potential devastating consequences for both the extremity and life of the patient. The authors present herein a rare case of self-induced subcutaneous emphysema of the thigh in a young patient, which resulted in aggressive management consisting of IV antibiotics, hyperbaric oxygen therapy, and surgical debridement. Correlation of the various findings of the history, physical examination, imaging and laboratory findings is critical in order to avoid unnecessary radical treatment. In the absence of an apparent cause, factitious disorder should always be considered.

Childhood trauma history and dissociative experiences among Turkish men diagnosed with antisocial personality disorder.

OBJECTIVE: This study investigated the association between antisocial personality disorder (APD), childhood trauma history, and dissociative symptoms in a sample of Turkish recruits. METHODS: A total of 579 male patients diagnosed with APD were examined in a military hospital setting. An age and gender matched control group of 599 normal persons with no known medical or psychiatric disorder were also chosen among military personnel. The subjects were evaluated with an assessment battery using a semi-structured interview for socio-demographic characteristics, APD section of SCID-II, an adapted version of the Structured Trauma Interview, and Dissociative Experiences Scale. RESULTS: Childhood sexual abuse, physical abuse, neglect, and early separation from parents were significantly more common among antisocial subjects than among controls. APD group reported significantly more dissociative symptoms and 50.4% of them reported pathological level of dissociation. Overwhelming childhood experiences of all four types were significant predictor of the APD diagnosis. Analyses also showed that childhood traumatic events and comorbid psychopathological features relevant to antisocial personality were significantly associated with pathological level of dissociation. CONCLUSION: These results revealed the importance of inquiring about patient's history of childhood traumatization and dissociative experiences when diagnosed with APD.

Clinical predictors of therapeutic response to clozapine in a sample of Turkish patients with treatment-resistant schizophrenia.

BACKGROUND: Several lines of evidence suggest that clozapine is more effective than both first- and second-generation antipsychotic drugs in treatment-resistant schizophrenia (TRS). However, clinicians appear to be hesitant to prescribe this drug. It would therefore be extremely valuable if predictors of response to clozapine could be identified. The aim of this study was to evaluate the predictive factors of clinical responses to clozapine in a group of Turkish patients with TRS. METHODS: This was a 16-week uncontrolled open study carried out among 97 TRS patients (80 males and 17 females; DSM-IV diagnosis). All patients fulfilled the criteria for refractory schizophrenia according to the UK guidelines for the National Institute of Clinical Excellence (NICE). After all previous antipsychotic medications had run their course, the patients were started on clozapine according to a standardized titration and dosage schedule. Psychopathology was evaluated before the initiation of clozapine therapy and once every 4 weeks using the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment for Positive Symptoms, and the Scale for the Assessment of Negative Symptoms. RESULTS: Of the TRS patients on clozapine, 55.7% achieved a clinical response, defined as at least a 20% decrease in BPRS. We observed a favorable effect of clozapine on both positive and negative symptoms. Logistic regression analysis showed that a good clozapine response was more likely when schizophrenia began at a later age, when negative symptoms were severe, and when patients had an early response at 4 weeks. CONCLUSION: A combination of demographic, baseline clinical, and acute treatment response variables may accurately predict response to clozapine in TRS. Priority should be given to initiating clozapine at the earliest phase of TRS, especially for patients with evident negative symptoms.

Panic disorder due to ingestion of single dose ecstasy.

Ecstasy or MDMA (3,4 methylenedioxymethamphetamine) is a popularly consumed substance worldwide. There have been various reports documented in the literature that have attributed MDMA to precipitating the onset of a wide range of persistent psychiatric symptoms. Additionally, there is increasing evidence of a permanent injury to the serotonergic neurons. In this case report, a person demonstrating panic disorder after the ingestion of a single dose of MDMA is described and potential mechanisms of action are reviewed.

Leptospirosis presenting with mania and psychosis: four consecutive cases seen in a military hospital in Turkey.

OBJECTIVE: To present the clinical features and the treatment alternatives of manic and psychotic symptoms in patients with leptospirosis. METHODS: Clinical observation and diagnosis of four cases with leptospirosis presenting with psychiatric symptoms. RESULTS: Leptospirosis diagnoses were established by recovery of the organism from culture, macroagglutination tests, and dark field microscopy in all cases. Leptospira ELISA-Ig M was also positive in all cases. Microagglutination tests were positive in case 1 and case 2. All of the cases were also screened for other possible medical, infectious, and neurological disorders that could account for their clinical symptoms. Patients were treated with a combination of antibiotics, antipsychotics and mood stabilizers. CONCLUSIONS: The presence of manic and psychotic symptoms with fever and high transaminase and/or CPK levels in high risk occupational groups during rainy periods should alert the physician to the possibility of leptospirosis. The psychiatric symptoms are sensitive to anti-psychotics and mood stabilizers but not to antimicrobial treatment, suggesting that the psychiatric picture may not be related to direct invasion of the central nervous system by the infectious agent.