Association between serotonin 2A receptor (HTR2A), serotonin transporter (SLC6A4) and brain-derived neurotrophic factor (BDNF) gene polymorphisms and citalopram/sertraline induced sexual dysfunction in MDD patients.

Sexual dysfunction (SD) is a troublesome adverse effect of selective serotonin reuptake inhibitors (SSRIs). A variety of mechanisms might be involved in the occurrence of SD but the exact mechanism is still not clear. Genetic variations among patients treated with SSRIs are strong determinants of intolerance and poor compliance. The present study aimed to determine the relationship between serotonin-2A receptor (HTR2A) gene -1438A/G and 102T/C polymorphisms, serotonin transporter gene (SLC6A4) 5-HTT-linked polymorphic region (5-HTTLPR) insertion/deletion variant and brain-derived neurotrophic factor (BDNF) gene Val66Met polymorphisms and the occurrence of SD adverse effect in major depressive disorder patients treated with citalopram (CIT) or sertraline (SERT). The result from this investigation revealed that the -1438A/G and 102T/C polymorphisms appear to be associated with the SD induced by CIT. It was also demonstrated that patients receiving SERT, carrying T allele of HTR2A or L allele of 5-HTTLPR more likely to experience SD. Most important overall finding of the study is the combined effects of -1438A/G, 102T/C, and 5-HTTLPR polymorphisms. In a logistic regression model, the occurrence of SD increased with the number of risky alleles. As compared with subjects receiving SERT with few risky (≤2) alleles, those with had 5-6 alleles had an increased SD risk. After all, according to these findings, -1438A/G, 102T/C, and 5-HTTLPR polymorphisms could be considered as promising pharmacogenetic biomarkers in CIT/SERT treatment in major depressive disorder (MDD) patients to avoid the occurrence of SD.

Theory of Mind in Schizophrenia and Asperger's Syndrome: Relationship with Negative Symptoms.

OBJECTIVE: Although previous studies have shown that the theory of mind (ToM) ability is impaired in Asperger's Syndrome (AS) and in schizophrenia, few controlled studies compared the ToM performance between the two disorders. Besides, the relationship between the degree of ToM impairment and symptom dimensions is unclear, and presence of ToM impairment in remitted patients with schizophrenia is controversial. Here, we tested the hypothesis that schizophrenia patients with prominent negative symptoms were closer to AS patients and different than schizophrenia patients without prominent negative symptoms and healthy controls in terms of ToM functioning. METHOD: Fourteen patients with AS, 20 with schizophrenia and 20 healthy controls, matched by age, educational level and IQ scores were enrolled. AS was diagnosed according to the DSM-IV criteria and independently confirmed by two psychiatrists. Schizophrenia patients were diagnosed by the Turkish version of Structured Clinical Interview for DSM-IV Diagnosis (SCID-I) and symptom severity was evaluated with the Scale for the Assessment of Negative and Positive Symptoms. Schizophrenia group consisted of clinically stable patients. The ToM battery included stories to assess first and second order false belief tasks (ToM1 and ToM2). The full-scale IQ, Verbal Comprehension, Freedom from Distractibility and Perceptual Organization scores were assessed by Weschler Adult Intelligence Scale-Revised (WAIS-R). Non-parametric tests were used to compare the neuropsychological performances of the three groups. In order to investigate whether schizophrenia patients with prominent negative symptoms were similar to AS patients, schizophrenia patients were divided into high (Sch-HN) and low (Sch-LN) negative-symptom subgroups by median split. For these four groups (AS, Sch-HN, Sch-LN, and controls) between group comparisons were performed. Correlations between the clinical measures and ToM performance were assessed by Spearman correlation test. RESULTS: AS and schizophrenia patients performed significantly worse than controls in the ToM2 task, while the AS group had worse ToM1 performance than both schizophrenia patients and healthy controls. The Sch-HN subgroup had significantly lower ToM2 scores than the Sch-LN patients, and worse ToM1 functioning than the controls. CONCLUSIONS: These results suggest that clinically stable schizophrenia patients have ToM impairments. Sch-HN group performed comparably poorly as the AS group, while the Sch-LN group was relatively spared. The most profoundly impaired patients with schizophrenia in terms of ToM functioning were represented by those with high negative symptoms (Sch-HN). Similar to AS, as a neurodevelopmental impairment, these patients may not have developed ToM ability, or they may have lost their ToM capacity as a result of a neurodegenerative process during the illness. Supplementary studies using other methods (e.g., neuroimaging, neurophysiology) may highlight the brain regions that are affected differentially in AS and schizophrenia, the relationship of ToM impairments and negative symptoms, and the role of ToM impairments in the neurodevelopmental or neurodegenerative hypothesis of schizophrenia.

[Proton magnetic resonance spectroscopy in Asperger's syndrome: correlations with neuropsychological test scores]. / Asperger Sendromunda Proton Manyetik Rezonans Spektroskopi: Nöropsikolojik Testlerle Iliskisi.

OBJECTIVES: It has been shown that autistic spectrum patients have impaired theory of mind (ToM) performance; however, no study has investigated the relationship between ToM performance and brain neurochemistry in these patients. The present study aimed to investigate the correlations between dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) N-acetyl-aspartate (NAA)/choline (Cho), NAA/creatine (Cr), and Cho/Cr values based on 1H magnetic resonance spectroscopy and ToM tests. METHOD: The study sample included 13 adult, right-handed, Caucasian males with Asperger's syndrome (AS) (age range: 17-37 years) and 20 controls matched by age, gender, handedness, and Wechsler Adult Intelligence Scale, Revised (WAIS-R) full-scale IQ scores. RESULTS: AS cases had significantly lower ToM performance. DLPFC NAA/Cho levels were inversely correlated to ToM scores (r = -0.738, P = 0.004). On the other hand, ToM performance improved as DLPFC Cho/Cr increased (r = 0.656, P = 0.015). ACC MRS variables were not significantly correlated with ToM performance in the AS group. No significant correlation was observed between ACC or DLPFC MRS variables and ToM performance in the control group. DISCUSSION: Because NAA/Cho was inversely correlated with ToM performance and Cho/Cr was correlated with ToM performance, it can be suggested that the Cho level was related to better ToM test performance in the AS group. An increase in the Cho peak was associated with an increase in membrane breakdown or turnover. The Cho peak was also thought to reflect cellular density and astrocytosis. It is suggested that membrane turnover and astrocytosis might affect cognitive functioning.

A Very Rare Adverse Effect of Clozapine, Clozapine-induced Interstitial Lung Disease: Case Report and Literature Review.

Clozapine is the gold-standard antipsychotic agent for treatment-resistant schizophrenia. Yet with all its clinical efficacy, there are numerous adverse effects associated with clozapine. Although many, such as leucopenia and agranulocytosis, are well established, there is little published material on the drug's rare adverse effects. Among these, very little is known about clozapine-induced interstitial lung disease. Here we present such a case. We focus on its clinical aspects and discuss its relationship to the extant literature.

Prefrontal Activity Measured by Functional Near Infrared Spectroscopy During Divergent and Convergent Thinking in Bipolar Disorder.

INTRODUCTION: Biographical research as well as some controlled studies point out to a relationship between bipolar disorder (BD) and creativity. Neurobiological underpinnings of this relationship are unclear. Although there is no consensus on the definition of creativity, Alternative uses Test (AuT) and Remote Association Test (RAT) are frequently used to measure convergent and divergent creativity. We aimed to examine prefrontal cortex (PFC) activity with functional near-infrared spectroscopy (fNIRS) during the RAT and AuT tests in subjects with BD. METHODS: We measured PFC activity in subjects with remitted BD (N=31) and healthy control subjects (N=27) with fNIRS during divergent and convergent thinking tasks (AuT and RAT respectively). We were particularly interested in the antero-posterior dissociation of the activity within the PFC according to the two task domains. RESULTS: We found that the index subjects displayed lower performance than healthy controls during the AuT and the RAT. AuT and RAT were associated with different activities in the two groups. Anterior PFC (aPFC) activity was higher than posterior PFC (pPFC) activity during the RAT in the index group, and during the AuT in the control group. aPFC activity was negatively correlated with the RAT performance in the index group. CONCLUSION: Higher activity in the aPFC may be the functional neuro-anatomical correlate of low convergent creativity performance in BD.

Frontal activity during a verbal emotional working memory task in patients with Alzheimer's disease: A functional near-infrared spectroscopy study.

Emotional working memory (EWM) is suggested as a working memory (WM) type, distinguished to process emotional stimuli, and may or may not be spared in Alzheimer's disease (AD). The aim was to compare patients with AD and healthy older adults (HC) on verbal EWM performance and accompanying prefrontal cortex activity. Twenty AD patients along with 20 HC individuals are required to complete an emotional one-back task in three conditions (neutral, positive and negative word lists). Prefrontal oxyhemoglobin (oxyHb) concentrations were measured simultaneously by a 24- channel functional near infrared spectroscopy device. Correct response rates were similar in two groups in all conditions. Reaction times were comparable in the EWM positive condition but longer in the AD group in EWMneutral and negative conditions. In the HC group, emotional words had no significant effect on WM. On the other hand, positive compared to neutral words led to greater activation in the left ventral prefrontal cortex (VPFC) in AD group. When compared to HCs, activity in the VPFC was significantly higher in AD patients during the positive condition. Positive words facilitated WM performance in participants with AD. Activity in VPFC may be the functional correlate of this phenomenon.

Prefrontal activity measured by functional near infrared spectroscopy during probabilistic inference in subjects with persecutory delusions.

Jumping to conclusions (JTC) is a probabilistic reasoning bias and is thought to contribute to delusion formation. Neurobiological correlates of the JTC bias are not known. We aimed to examine the rostral prefrontal cortex (rPFC) activity with functional near infrared spectroscopy during a modified version of the Beads in a Jar Task (BIJT) in subjects with persecutory delusions (N=25). In BIJT participants are presented beads either drawn from one of the two jars with opposite probability ratios (PRs) of colored beads and are required to decide from which jar beads are being drawn. We administered the BIJT with 90/10 and 55/45 PRs. Compared to healthy controls (N=20), patients reached a decision earlier in both conditions. While the medial rPFC regions were more active in the 90/10 condition in controls compared to patients, lateral rPFC activation was higher in the 55/45 condition in patients than controls. Only in the control group, there was a marked decline in the lateral rPFC activation in the 55/45 condition compared to the 90/10 condition. The activity in the lateral rPFC was negatively correlated with the amount of beads drawn in healthy controls but not in subjects with persecutory delusions. Our results suggest that during the BIJT, rPFC does not function as a single unit and rather consists of functional subunits that are organized differently in patients and controls. The failure to deactivate the lateral rPFC may be associated with earlier decisions in subjects with persecutory delusions.

Liebowitz Social Anxiety Scale: the Turkish version.

The present study aimed at establishing the Turkish version of the Liebowitz Social Anxiety Scale. For this aim interrater, test-retest, and internal reliability coefficients of the Turkish version were assessed as well as its convergent, discriminant, and criterion validity. Subjects were 88 patients with the diagnosis of generalized social phobia, 40 patients with a diagnosis of anxiety disorders other than generalized social phobia, and 40 people had no diagnosis of psychopathology. All reliability assessments indicated good reliability. For convergent and discriminant validity, correlations of 3 scores (2 subscales and the whole scale) and the Beck Anxiety Inventory were examined. Consistent with the expectations of the discriminant validity, correlations based on the whole sample were not significant. On the other hand, consistent with the expectations of the convergent validity, when patients with the diagnosis of generalized social phobia were considered, all the correlations were significant. Finally, the criterion validity of the Turkish version indicated that all 3 scores discriminated patients with the diagnosis of generalized social phobia, not only from the people who were free of psychopathology but also from the patients with the diagnosis of anxiety disorders other than generalized social phobia. Findings were discussed in the light of literature.

Total exposure duration and proximity of cessation of cannabis use predict severity of sub-clinical psychotic symptoms among former users.

In a non-clinical military enrolment setting, former cannabis users (N=81), compared to substance-naïve controls (N=132), endorsed markedly elevated rates of schizotypy subscale scores on the Schizotypal Personality Questionnaire (SPQ). Total duration of exposure and proximity of cessation of cannabis use also had an important impact on the severity of psychosis-like symptoms.

[The relationship between right hemi-space visuospatial attention disturbance and anger in antisocial individuals]. / Antisosyal bireylerde sag yari uzaya iliskin görsel dikkat bozukluguyla öfkenin iliskisi.

OBJECTIVE: Evidence suggests that individuals with antisocial personality disorder (APD) exhibit a less asymmetric pattern than healthy controls during auditory and visuospatial attention tasks characterized by a right hemispheric advantage; however, the association between attention asymmetry and symptomatology is not clear. The present study aimed to examine the relationship between visuospatial attention in the right and left hemi-spaces, and various dimensions of anger in individuals with APD. MATERIALS AND METHODS: We compared visuospatial attention performance in the right and left hemi-spaces during a computerized Line Bisection Test (LBT) in individuals with APD (n = 52) and healthy controls (n = 34). We also administered the Multi-Dimensional Anger Scale (MDAS) to both groups. RESULTS: Subjects in the APD group made larger bisection errors than healthy controls only during the right hemi-space condition and had higher scores than those in the control group on all MDAS dimensions of anger. The severity of anger symptoms and thoughts were predicted by right hemi-space visuospatial attention disturbance in the APD group, whereas no such association was observed in the control group. CONCLUSION: The present findings either suggest a left hemisphere neuropathology or a disturbance in inter-hemispheric transmission in the APD group. Right hemi-space-specific visual attention disturbance may mediate the relationship between neuropathology, and somatic and trait dimensions of anger in APD.

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.

The psychological effects of parental mental health on children experiencing disaster: the experience of Bolu earthquake in Turkey.

Disasters affect families as a whole, and symptoms displayed by a family member may lead to secondary traumatizations for other members of the family, especially the children. This study examines the effects of parental psychopathology and family functioning on children's psychological problems six months after the earthquake in Bolu, Turkey. Forty-nine children aged between 7 and 14 and their parents were randomly chosen from among 800 families living in a survivor camp in Bolu. Both the children and parents were assessed by trained psychiatrists and psychologists using self-report measures for posttraumatic stress disorder (PTSD), depression, and anxiety symptoms six months after the earthquake. Family functioning in survivor families was also assessed using the Family Assessment Device (FAD). The results showed that the severity of PTSD in children was mainly affected by the presence of PTSD and the severity of depression in the father. State and trait anxiety scores of children were related to general family functioning. The constellation of PTSD symptomatology was different in fathers than in mothers: the most common type of symptoms was "externalizing" in fathers with PTSD. This study supports the notion that the mere presence of PTSD in parents may not be enough to explain the relational process in families experiencing trauma. Our findings with earthquake survivors suggest that when fathers become more irritable and detached because of PTSD symptoms, their symptoms may affect children more significantly.