Higher schizotypy predicts better metabolic profile in unaffected siblings of patients with schizophrenia.

RATIONALE: Type 2 diabetes (T2D) is more frequent in schizophrenia (Sz) than in the general population. This association is partly accounted for by shared susceptibility genetic variants. OBJECTIVE: We tested the hypotheses that a genetic predisposition to Sz would be associated with higher likelihood of insulin resistance (IR), and that IR would be predicted by subthreshold psychosis phenotypes. METHODS: Unaffected siblings of Sz patients (n = 101) were compared with a nonclinical sample (n = 305) in terms of IR, schizotypy (SzTy), and a behavioural experiment of "jumping to conclusions". The measures, respectively, were the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), Structured Interview for Schizotypy-Revised (SIS-R), and the Beads Task (BT). The likelihood of IR was examined in multiple regression models that included sociodemographic, metabolic, and cognitive parameters alongside group status, SIS-R scores, and BT performance. RESULTS: Insulin resistance was less frequent in siblings (31.7%) compared to controls (43.3%) (p < 0.05), and negatively associated with SzTy, as compared among the tertile groups for the latter (p < 0.001). The regression model that examined all relevant parameters included the tSzTy tertiles, TG and HDL-C levels, and BMI, as significant predictors of IR. Lack of IR was predicted by the highest as compared to the lowest SzTy tertile [OR (95%CI): 0.43 (0.21-0.85), p = 0.015]. CONCLUSION: Higher dopaminergic activity may contribute to both schizotypal features and a favourable metabolic profile in the same individual. This is compatible with dopamine's regulatory role in glucose metabolism via indirect central actions and a direct action on pancreatic insulin secretion. The relationship between dopaminergic activity and metabolic profile in Sz must be examined in longitudinal studies with younger unaffected siblings.

Identifying gene-environment interactions in schizophrenia: contemporary challenges for integrated, large-scale investigations.

Recent years have seen considerable progress in epidemiological and molecular genetic research into environmental and genetic factors in schizophrenia, but methodological uncertainties remain with regard to validating environmental exposures, and the population risk conferred by individual molecular genetic variants is small. There are now also a limited number of studies that have investigated molecular genetic candidate gene-environment interactions (G × E), however, so far, thorough replication of findings is rare and G × E research still faces several conceptual and methodological challenges. In this article, we aim to review these recent developments and illustrate how integrated, large-scale investigations may overcome contemporary challenges in G × E research, drawing on the example of a large, international, multi-center study into the identification and translational application of G × E in schizophrenia. While such investigations are now well underway, new challenges emerge for G × E research from late-breaking evidence that genetic variation and environmental exposures are, to a significant degree, shared across a range of psychiatric disorders, with potential overlap in phenotype.

[Science, Psychiatry, and the DSM]. / Bilim, Psikiyatri, DSM'ler.

The upcoming publication of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), provides an opportunity to revisit the seldom-addressed methodological issues in contemporary psychiatry. We think that DSM widely determines the scientific and clinical orientation of the discipline, and therefore provides a good vantage point to critique the current psychiatric methodology. The main scientific problem is a perseverative attempt at validating descriptively defined disorders that are standardized and simplified to achieve diagnostic reliability. Lack of a single psychiatric phenomenon that is valid, i.e. natural, for initiating any reduction limits research to inductive-probabilistic methods, basically correlational analyses. Furthermore, reduction in psychiatry is typically directed at basic sciences, neglecting general medical diagnoses as possible intermediary correlates. The subcategory "Due to a General Medical Condition" is elusive, and the biopsychosocial approach does no more than strengthen the brain-disease illusion surrounding DSM definitions by justifying psychiatry as a branch of medicine while failing to stipulate detailed medical assessment and discouraging psychopathology-based clinical reasoning. It is therefore no surprise that, although our understanding of the neural basis and mechanisms of behavior has improved along with advances in the neurosciences, not a single DSM disorder has been validated by the discovery of a specific cause, pathophysiology, or structural abnormality since the adoption of the descriptive approach in 1980. New knowledge involves single traits or dimensions of mood, thought, or behavior, none of which are specific to any disorder. The optimum approach today would be to redefine the discipline as neuropsychiatry.

[Fragile X premutation in adult psychiatry: four cases and overview of clinical presentation]. / Eriskin Psikiyatrisinde Frajil X Premutasyonu: Dört Vaka Sunumu ve Klinik Görünümün Tanitimi

Fragile X carrier status, also named as Fragile X premutation (FraX-PM), is defined by trinucleotide repeat expansions of shorter length compared to those that cause the full syndrome. Its clinical significance has been limited to the risk of further expansion to a full mutation in the offspring of carriers, until it was recently recognized as a clinical syndrome on its own, manifested by unique symptom constellations, as well as a combination of neuropsychiatric signs and symptoms that may be indistinguishable from several commonly seen disorders. The complex heterogeneity of its neuropsychiatric manifestations may render the diagnosis challenging, unless the clinician is familiar with the clinical picture and transmission pattern. We present four cases of FraX-PM, diagnosed in an adult psychiatry setting and confirmed by genetic testing. The aim of this report is to increase familiarity among psychiatric practitioners, since this common condition is seldom included in the current diagnostic practice, which is based on atheoretical definitions.

Defibrillation testing and early neurologic outcome.

During implantable cardioverter-defibrillator (ICD) implantation, ventricular defibrillation testing (DFT) is considered a standard procedure. This procedure often requires multiple ventricular fibrillation (VF) inductions. These repeated short episodes of circulatory arrest with global cerebral ischemia may cause neurological damage. In the present study, patients undergoing initial ICD implantation and limited induction of VF for defibrillation safety margin testing were evaluated for pre- and postoperative cognitive and neurologic functions. In addition, the serum neuron specific enolase (NSE) level, which is a biochemical marker of cerebral injury, was evaluated. The study was performed on 16 patients undergoing initial elective transvenous insertion of an ICD. A neurologic examination and cognitive assessment tests were performed 24 to 48 hours before and after ICD. NSE was determined before (NSE 1) and at the end of the surgery (NSE 2), as well as 2 hours (NSE 3), 24 hours (NSE 4), and 48 hours (NSE 5) after implantation. A total of 29 internal shocks (average, 1.8 +/- 0.4) with energy ranging from 14 to 41 J (mean, 20 +/- 5; median, 20 J ) were delivered in the ICD group patients. In one patient, 3 external (50, 200 and 360 J) shocks were required for fast VT induced during ICD lead positioning. The mean duration of VF was 10 +/- 4 seconds and the mean cumulative time in VF was 16 +/- 5 seconds. The mean recovery time between VFs was 5.3 +/- 0.6 minutes. NSE levels were not different from the baseline at any time point in the patients of the group that completed the 48-hour observation period (P > 0.05). The patients did not report any new neurological symptoms after ICD implantation, and repeat examination after the procedure showed no abnormal findings other than those detected in the previous one. There were no statistically significant differences between the preoperative and postoperative scores obtained in the cognitive assessment. Single or two VF inductions and the brief arrest of cerebral circulation during ICD implantation are not associated with permanent neurological injury. However, further studies are needed to confirm this finding.

Peculiar word use as a possible trait marker in schizophrenia.

Peculiar word use in schizophrenia has been emphasized by many authors, however the definition or the linguistic and clinical correlates of this phenomenon are not clear. We propose a new, standard and reliable method to extract a numerical measure of peculiar word use with operationalized definitions. We applied a modified version of the Controlled Word Association Test (Turkish version) to a pool of healthy subjects (N=55) and used the data as norm to compare the degree of peculiarity and patterns of word association among patients with schizophrenia (N=33), their healthy siblings (N=31) and healthy controls (N=32). We also explored the relationship of peculiar word use with patterns of word association (semantic versus phonologic) and formal thought disorder. Patients and their siblings performed worse on measures of verbal fluency. They also generated more peculiar words and relied less on semantic associations, compared to healthy controls. Peculiar word use was associated with the severity of formal thought disorder and the tendency to make use of phonologic associations in the patient group and their siblings, whereas neither of the word association patterns predicted peculiar word use in the control group. Our results provide empirical support to previous observations about the peculiarity of schizophrenic speech. Peculiar word use could be associated with a deficit to employ semantic classifications in verbal fluency tasks and thus relying more on sound-based associations. Excess use of phonologic associations may be playing a mediating role between semantic processing abnormalities and formal thought disorder.

[The factor structure of schizophrenic symptoms: which model is supported by independent item analysis?]. / Sizofreni belirtilerinin faktör yapisi: bagimsiz madde analizi nasil bir modeli destekliyor?

OBJECTIVE: Most studies that have investigated the symptom dimensions of schizophrenia utilizing the Scale for the Assessment of Positive Symptoms (SAPS) and the Scale for the Assessment of Negative Symptoms (SANS), both global rating scales, favored a 3-factor model. Only a few studies have examined the factor structure at the item level and they suggest a wider dimensional structure. The factor structure of schizophrenic symptoms has not been previously studied in Turkey, nor has the construct validity of these scales. The present study sought to determine the factor structure of the independent items and the construct validity of the scales. METHOD: The study included 180 schizophrenia patients (diagnoses based on DSM-IV criteria). The standard statistical methods of principal component analysis (PCA) and varimax rotation were used to extract factors. RESULTS: PCA of the global items yielded a 3-factor solution, representing positive, negative, and disorganization dimensions. Item-level factor analysis revealed 12 factors: Psychomotor poverty, positive formal thought disorder, auditory/visual hallucinations, social and occupational dysfunction, bizarre delusions, attention/stereotypy, paranoid features, somatic hallucinations/delusions, appearance, grandiose/religious delusions, inappropriate affect, and delusions of jealousy. CONCLUSION: Consistent with previous studies, neither the global nor the item-level factor structures supported the simple positive-negative dichotomy or the composition of the sub-scales; therefore, future studies should make use of the single items, especially when positive symptoms are being studied.

Impaired verbal memory and otherwise spared cognition in remitted bipolar patients on monotherapy with lithium or valproate.

OBJECTIVES: Patients with bipolar disorder have been reported to have neurocognitive deficits; however, it is not known whether the cognitive dysfunctions are state-dependent or a stable trait. Lithium and valproate, 2 of the most widely used mood stabilizers in the treatment of bipolar disorder, have also been associated with cognitive impairment. However, the degree and pattern of neurocognitive impairment in euthymic bipolar patients on either monotherapy with lithium or valproate have not been compared before in depth. METHODS: We compared 17 euthymic outpatients with bipolar disorder (BD) on lithium monotherapy to 11 euthymic outpatients with BD on valproate monotherapy and 29 comparison subjects using tests measuring immediate verbal memory and executive functions in addition to 3 subtests of the Wechsler Adult Intelligence Scale Revised. The groups were similar in terms of level of education, duration and severity of illness, and gender distribution. Patients on lithium monotherapy were older than patients on valproate and healthy controls. Mood symptoms as assessed by standardized scales were mild to non-existent in both patient groups. RESULTS: Immediate verbal memory was impaired in both patient groups compared to controls, where the main effect of age was not significant. No significant differences could be found on the other cognitive measures. CONCLUSIONS: Both lithium and valproate may be associated with immediate verbal memory impairment, sparing other cognitive functions. Presence of a similar verbal memory deficit in the lithium and valproate groups suggests that this deficit might be intrinsic to BD or that the 2 medications influence immediate verbal memory similarly. Larger samples of remitted bipolar patients on monotherapy should be studied for more precise conclusions.

The effectiveness of intramuscular biperiden in acute akathisia: a double-blind, randomized, placebo-controlled study.

Neuroleptic-induced acute akathisia (NIA) is a distressing condition and an important clinical problem because it is associated with treatment noncompliance and suicidal or impulsive behavior. Anticholinergics are among the treatment options; however, a review of the literature fails to identify a double-blind, randomized, placebo-controlled study of these medications in NIA. In a randomized, double-blind, placebo-controlled design, we studied the effectiveness of intramuscular biperiden (n = 15) or isotonic saline (n = 15) in the treatment of NIA diagnosed with the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria. Injections were repeated up to 3 times unless akathisia was completely treated (scored 0 for global akathisia with the Barnes Akathisia Rating Scale). Patients were assessed for akathisia, other movement disorders, and psychiatric symptoms at baseline and 3 times after the first injection at 2-hour intervals. Response was defined as at least a 2-point decline in the global akathisia score. The numbers of responders in the 2 groups were not significantly different (7 and 5 in the biperiden and placebo groups, respectively). The courses of individual items on the Barnes Akathisia Rating Scale were also similar. Our results suggest that intramuscular biperiden should not be considered as a first-line treatment of NIA.

Cortical inhibition in first-degree relatives of schizophrenic patients assessed with transcranial magnetic stimulation.

Although cortical inhibition deficit has been shown in schizophrenia patients by transcranial magnetic stimulation (TMS), some controversies remain, possibly due to confounding factors such as medication use and clinical state at the time of assessment. First-degree relatives of schizophrenia patients, who share various degrees of genetic vulnerability with the patients, but are free from confounds related to medication and/or florid psychosis, have not been studied to date. We compared 12 relatives with 14 controls on several paradigms with TMS. Three of the 12 healthy relatives lacked transcallosal inhibition (TI) in one or more of the stimulation levels. There were no significant differences in other parameters. The lack of TI in 25% of the relatives is an important finding that needs to be replicated in larger samples that are heterogeneous in terms of psychosis-proneness.

Relative sparing of executive functions in the early phase of schizophrenia.

Findings about the impairment of executive functions in schizophrenia are not conclusive. The authors hypothesized that the severity of the impairments in the abilities that comprise EF might be different. Forty patients were assessed with a comprehensive battery that included four measures of executive functions and were compared with 60 healthy subjects. Set shifting and response inhibition showed no significant between-group differences. Mental flexibility and concept formation were significantly worse in patients, but the effect sizes were small. Some executive functions might be relatively spared, at least in the early phase of schizophrenia. Studies on individual executive functions may yield more replicable findings.

Dissociation between inattentiveness during mental status testing and social inattentiveness in the Scale for the Assessment of Negative Symptoms attention subscale.

The Scale for the Assessment of Negative Symptoms (SANS) attention subscale has been found valid and reliable by some studies; however, there is some evidence to the contrary. We hypothesized that social inattentiveness (SANS 22) and inattentiveness during mental status testing (SANS 23) might be describing discrete constructs, and this dissociation might be a source of controversy. Thirty-five patients with DSM-IV schizophrenia were assessed by the Scale for the Assessment of Positive Symptoms (SAPS), SANS and a neuropsychological battery. The 2 attention items were not significantly interrelated. SANS 22 was correlated with bizarre behavior and alogia, and none of the neuropsychological test scores, whereas SANS 23 showed strong correlations with the Wechsler Memory Scale mental control subscore, total errors on the Benton Revised Visual Retention Test, and the information, similarities and the general verbal subscores on the Wechsler Adult Intelligence Scale. Regression analyses showed that SANS 23 could be a good estimate of general verbal abilities. These findings point to a dissociation between the 2 SANS attention items. Similar analyses should be repeated in larger and heterogeneous samples and include a factor analysis of the individual items rather than the global ratings.

[Reliability and validity of Turkish version of magical ideation scale in university students]. / Büyüsel düsünce olçegi'nin Türkçe formunun universite ogrencilerindeki geçerlik ve güvenilirligi.

OBJECTIVE: Schizoptypal disorder shares many clinical, neuropsychological and neurophysiological features with schizophrenia and is included in the schizophrenia spectrum. Patients with schizotypal disorder or individuals with mild schizotypal features are therefore highly valuable in the study of neuropsychological and neurophysiological characteristics of psychosis, and in particular schizophrenia, as they are likely to be free of the potential confounding factors of medication, chronic hospitalization and manifest psychosis. We report here the psychometric properties of the Turkish version of the Magical Ideation Scale (MIS), a self-report questionnaire that focuses on delusion-like beliefs and hallucination-like experiences and that has been used to quantify an important dimension of schizotypy. METHOD: Internal consistency and high cut-off scores were studied in 332 medical students. Forty-three students were readministered the scale 3 weeks later, and 96 received the Paranormal Belief Scale-R (PBS-R) along with the MIS, in order to measure test-retest reliability and convergent validity, respectively. RESULTS: The internal consistency of the scale is satisfactory with a Cronbach alpha coefficient of 0.78. Test-retest scores are highly correlated (r= 0.84). The high cut-off score is 21 for males, 23 for females, and 22 for the whole sample. Convergent validity was established by the significant correlation between the total MIS and PBS-R scores (r= 0.61). CONCLUSIONS: The scale is valid and reliable for studies that require a standard quantification of schizotypal signs and symptoms in young university students.