Long-term Outcomes of Intensive Inpatient Care for Severe, Resistant Obsessive-Compulsive Disorder: Résultats à long terme de soins intensifs à des patients hospitalisés pour un trouble obsessionnel-compulsif grave et résistant.

OBJECTIVE: A substantial proportion of severely ill patients with obsessive-compulsive disorder (OCD) do not respond to serotonin reuptake inhibitors (SRIs) and are unable to practice cognitive behavioral therapy (CBT) on an out-patient basis. We report the short-term (at discharge) and long-term (up to 2 years) outcome of a multimodal inpatient treatment program that included therapist-assisted intensive CBT with adjunctive pharmacotherapy for severely ill OCD patients who are often resistant to SRIs and are either unresponsive or unable to practice outpatient CBT. METHODS: A total of 420 patients, admitted between January 2012 and December 2017 were eligible for the analysis. They were evaluated using the Mini International Neuropsychiatric Interview, the Yale-Brown Obsessive Compulsive Scale (YBOCS), and the Clinical Global Impression (CGI) scale. All patients received 4 to 5 therapist-assisted CBT sessions per week along with standard pharmacotherapy. Naturalistic follow-up information at 3, 6, 12, and 24 months were recorded. RESULTS: At baseline, patients were mostly severely ill (YBOCS = 29.9 ± 4.5) and nonresponsive to ≥2 SRIs (83%). Mean duration of inpatient stay was 42.7 ± 25.3 days. At discharge, there was a significant decline in the mean YBOCS score (29.9 ± 4.5 vs. 18.1 ± 7.7, P < .001, Cohen's d = 1.64); 211/420 (50%) were responders (≥35% YBOCS reduction and CGI-I≤2) and an additional 86/420 (21%) were partial responders (25% to 35% YBOCS reduction and CGI-I≤3). Using latent class growth modeling of the follow-up data, 4 distinct classes were identified, which include "remitters" (14.5%), "responders" (36.5%), "minimal responders" (34.7%), and "nonresponders" (14.6%). Shorter duration of illness, better insight, and lesser contamination/washing symptoms predicted better response in both short- and long-term follow-up. CONCLUSION: Intensive, inpatient-based care for OCD may be an effective option for patients with severe OCD and should be considered routinely in those who do not respond with outpatient treatment.

Repetitive Transcranial Magnetic Stimulation Over Presupplementary Motor Area May Not Be Helpful in Treatment-Refractory Obsessive-Compulsive Disorder: A Case Series.

BACKGROUND: A significant proportion of patients with obsessive-compulsive disorder (OCD) fail to improve with standard medication and cognitive behavior therapy. Repetitive transcranial magnetic stimulation (rTMS) has been investigated for its role in treating OCD. Low-frequency rTMS over the presupplementary motor area (pre-SMA) has shown mixed results. Moreover, it has not been studied in highly treatment refractory OCD. We analyzed the outcome of low-frequency rTMS over pre-SMA in OCD patients refractory to multiple serotonin reuptake inhibitors (SRIs), augmenting agents, and cognitive behavior therapy. METHODS: Low-frequency (1-Hz stimulus at 100% motor threshold) rTMS was delivered over the pre-SMA using a previously described protocol. At least 25% reduction Yale-Brown Obsessive Compulsive Scale scores and 2-point reduction in Clinical Global Impression-Severity of Illness scores were used to assess treatment response. RESULTS: Seventeen patients were initiated on rTMS. Three of them dropped out within 9 sittings. Only 1 patient met the criteria for response after 1 month of treatment initiation. No major adverse effects were observed in any of them. LIMITATIONS: The study is a retrospective analysis of outcomes when rTMS was administered as part of routine clinical care. Assessments of the patients were done by trained but different raters, and interrater reliability was not measured. CONCLUSIONS: Low-frequency rTMS over the pre-SMA may not be effective in treatment refractory OCD. Further studies, taking note of the possible reasons for ineffectiveness discussed in the study, may help elucidate the role of rTMS in OCD.

An epidemological study of obsessive compulsive disorder in adolescents from India.

OBJECTIVES: There is scarce data on the prevalence of OCD among adolescents in India. This study reports point prevalence of OCD among school students (age 12-18years) in the Kerala state of India and examines its association with ADHD, psychological distress, tobacco/alcohol abuse, suicide risk and history of sexual abuse. METHOD: 7560 students of 73 schools were self-administered the OCD subsection of Clinical Interview Schedule-Revised, the Composite International Diagnostic Interview (CIDI) for obsessive compulsive symptoms and other relevant instruments to identify OCD and related clinical measures. A diagnosis of ICD-10 OCD was derived through the CIS-R algorithm which required duration of at least 2weeks and at least a thought/behavior to be resisted along with a cut-off score for severity and impairment. RESULTS: In the sample, 50.3% were males with a mean age of 15.2years (range of 12-18years). The response rate was 97.3% (7380 valid responses). 0.8% (n=61) fulfilled criteria for OCD with a male predominance (1.1 vs. 0.5%, p=0.005). Prevalence was higher among Muslims and increased with age. Taboo thoughts (62.3%) and mental rituals (45.9%) were the commonest symptoms. Those with OCD had significantly higher suicidal thoughts (59 vs. 16.3%, p<0.01) suicide attempts (24.6 vs. 3.8%, p<0.01), ADHD (28 vs. 4%, p<0.001), sexual abuse (24.6 vs. 4.2%, p<0.01), and tobacco use (23 vs. 6.8%, p=0.01). They also reported greater psychological distress and poorer academic performance. CONCLUSIONS: OCD is common among adolescents in India. Its associations with ADHD, sexual abuse, psychological distress, poorer academic performance and suicidal behavior are additional reasons for it to be recognized and treated early.

Prevalence and clinical correlates of obsessive-compulsive disorder in schizophrenia.

Obsessive compulsive symptoms frequently occur in a substantial proportion of patients with schizophrenia. The term schizoobsessive has been proposed to delineate this subgroup of schizophrenia patients who present with obsessive-compulsive symptoms/disorder. However, whether this co-occurrence is more than just co-morbidity and represents a distinct subgroup remains controversial. A striking variation is noted across studies examining prevalence of obsessive-compulsive symptoms/disorder in schizophrenia patients and their impact on clinical profile of schizophrenia. Hence, in this study, we examined the prevalence of obsessive-compulsive symptoms/disorder in a large sample of consecutively hospitalized schizophrenia patients and compared the clinical and functional characteristics of schizophrenia patients with and without obsessive-compulsive symptoms/disorder. We evaluated 200 consecutive subjects with the DSM-IV diagnosis of schizophrenia using the Structured Clinical Interview for DSM-IV Axis I disorders, Positive and Negative Syndrome Scale, Yale-Brown Obsessive-Compulsive Scale, Brown Assessment of Beliefs Scale, Clinical Global Impression-Severity scale, Global Assessment of Functioning Scale, Family Interview for Genetic Studies and World Health Organization Quality of Life scale. The prevalence of obsessive-compulsive symptoms in patients with schizophrenia was 24% (n=48); 37 of them had obsessive-compulsive disorder (OCD) and 11 had obsessive-compulsive symptoms not amounting to a clinical diagnosis of OCD (OCS). Schizophrenia patients with OCS/OCD had an earlier age at onset of schizophrenia symptoms, lower positive symptoms score, higher co-morbidity with Axis II disorders, higher occurrence of OCD in family and better quality of life. Findings of the study indicate a higher prevalence of OCS/OCD in schizophrenia. Schizophrenia patients with and without OCS/OCD have comparable clinical profile with few exceptions. High rates of OCD in first degree relatives suggest possible genetic contributions and differences in neurobiology. Finally, evidence to consider schizoobsessive as a distinct diagnostic entity is inconclusive and warrants further studies.

Comparative efficacy of repetitive transcranial magnetic stimulation protocols for obsessive-compulsive disorder: A network meta-analysis.

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) has been found to be helpful for the treatment of obsessive-compulsive disorder (OCD). However, the relative efficacy of different rTMS protocols is unclear. OBJECTIVE: To conduct a systematic review and network meta-analysis (NMA) of published literature to compare the relative efficacy of different rTMS protocols for decreasing Yale-Brown Obsessive Compulsive Severity (Y-BOCS) scores in patients with OCD. METHOD: Relevant articles published between 1985 to September 2023 were searched from the Cochrane Central Register of Controlled Trials, PubMed and PsycInfo. Double or single-blinded randomized controlled studies conducted on patients with OCD comparing an active rTMS protocol with either another active or sham rTMS protocol were included. Network meta-analysis (NMA) was conducted using a frequentist approach. Standardized mean difference (SMD) of change in Y-BOCS scores was calculated employing Hedge's g. Pairwise meta-analysis using random effects model was conducted which was extended to the NMA using restricted maximum likelihood estimation procedure. Surface under the cumulative ranking (SUCRA) probabilities were used to rank the interventions. RESULTS: Excitatory rTMS of the bilateral dorsolateral prefrontal cortex (DLPFC), inhibitory rTMS of right DLPFC, inhibitory as well as excitatory rTMS of bilateral medial prefrontal cortex/anterior cingulate cortex (mPFC/ACC) and inhibitory rTMS of bilateral supplementary motor area (SMA) were superior to sham stimulation. The DLPFC and mPFC/ACC protocols had a higher probability of being among the top-ranked interventions. The majority of studies had a modest sample size and at least some concerns in the risk of bias assessment. CONCLUSION: rTMS targeting either the medial or lateral prefrontal cortices is a promising intervention for resistant OCD. There is a need to confirm these findings in large systematic studies.

Global multi-center and multi-modal magnetic resonance imaging study of obsessive-compulsive disorder: Harmonization and monitoring of protocols in healthy volunteers and phantoms.

OBJECTIVES: We describe the harmonized MRI acquisition and quality assessment of an ongoing global OCD study, with the aim to translate representative, well-powered neuroimaging findings in neuropsychiatric research to worldwide populations. METHODS: We report on T1-weighted structural MRI, resting-state functional MRI, and multi-shell diffusion-weighted imaging of 140 healthy participants (28 per site), two traveling controls, and regular phantom scans. RESULTS: Human image quality measures (IQMs) and outcome measures showed smaller within-site variation than between-site variation. Outcome measures were less variable than IQMs, especially for the traveling controls. Phantom IQMs were stable regarding geometry, SNR, and mean diffusivity, while fMRI fluctuation was more variable between sites. CONCLUSIONS: Variation in IQMs persists, even for an a priori harmonized data acquisition protocol, but after pre-processing they have less of an impact on the outcome measures. Continuous monitoring IQMs per site is valuable to detect potential artifacts and outliers. The inclusion of both cases and healthy participants at each site remains mandatory.

White matter abnormalities in children and adolescents with obsessive-compulsive disorder: a diffusion tensor imaging study.

BACKGROUND: There is paucity of data on white matter (WM) abnormalities in juvenile obsessive-compulsive disorder (OCD). This study aimed to identify WM microstructure changes in juvenile OCD. METHODS: Fifteen children and adolescents with OCD and 15 matched healthy controls underwent diffusion tensor imaging using a 3 Tesla (Achieva, Best, The Netherlands) magnetic resonance imaging scanner. Voxelwise analyses were conducted on data processed through tract-based spatial statistics (TBSS). RESULTS: Patients significantly differed from controls in axial as well as radial diffusivities, but not in fractional anisotropy. Patients demonstrated significantly increased axial diffusivity in corpus callosum (genu, body, and splenium), right and left superior longitudinal fasciculi, left inferior longitudinal fasciculus, right and left cingulum, bilateral anterior thalamic radiations, bilateral anterior limb of internal capsule, left posterior limb of the internal capsule, and middle cerebellar peduncle. In addition, significantly increased radial diffusivity was seen in patients in genu of the corpus, right and left superior longitudinal fasciculi, left inferior longitudinal fasciculus, right and left uncinate fasciculi, bilateral anterior thalamic radiation, bilateral inferior fronto-occipital fasciculus, left posterior limb of internal capsule, right superior cerebellar peduncle, middle cerebellar peduncle, and right inferior cerebellar peduncle. CONCLUSIONS: Our findings suggest involvement of multiple WM tracts in juvenile OCD. In addition to the widely proposed hypothesis of orbitofrontal-striato-thalamo-cortical circuitry deficits in the development of OCD, our findings suggest involvement of additional brain regions, possibly parietal cortex, lateral prefrontal cortex, and limbic system. The widespread differences in WM among cases and controls also points to the possibility of underlying myelination changes.

Obsessive-compulsive disorder with and without bipolar disorder.

AIM: Bipolar disorder (BD) is often comorbid with obsessive-compulsive disorder (OCD). In this study, we compared clinical profile and course of subjects with a primary diagnosis of OCD with and without BD. METHODS: We compared 34 subjects with primary diagnosis of OCD with BD and 57 subjects with a diagnosis of OCD without BD. Structured interview schedules, clinical rating scales, and information from clinical charts were utilized to assess patients. RESULTS: OCD with BD was characterized by: (i) an episodic course; (ii) a higher number of depressive episodes, greater suicidality and a higher rate of hospitalization; (iii) fewer pathological doubts and more miscellaneous compulsions; and (iv) poorer insight into obsessive-compulsive symptoms. CONCLUSIONS: Episodic course appears to be typical of OCD with BD. Bipolarity has a pathoplastic effect on OCD and it is possible that some forms of OCD and BD are pathophysiologically related. Bipolar OCD is associated with a higher rate of depressive episodes, higher suicidality and more frequent hospitalizations, suggesting greater morbidity. Long-term prospective follow-up studies and studies addressing pathophysiology and genetic basis are needed to understand the complexity of such comorbidity.

Naturalistic outcome of medication-naïve obsessive compulsive disorder treated with serotonin reuptake inhibitors.

OBJECTIVE: The data on the course of obsessive compulsive disorder (OCD) is mostly derived from studying chronic, severely ill patients with varying degree of treatment resistance. We studied the course and outcome of OCD patients who were medication-naïve at initial assessment compared to those who were medicated. MATERIAL AND METHODS: We analyzed the clinical chart data of all patients with a primary diagnosis of OCD attending a speciality OCD clinic in India during a specified period and compared outcome between medication-naïve (n = 75) and medicated (n = 117) patients. RESULTS: The mean time to remission was shorter in the medication-naïve [18.99 months (95 % CI: 14.61-23.37)] compared to medicated [33.91 months (95 % CI: 27.55-40.28)] patients. The survival distribution of the two groups was significantly different as per the log-rank test (χ2 = 5.76, p = 0.02). In the Cox proportional hazards regression, medication-naïve status predicted time to remission. Overall, the rate of remission was the same in both groups (57 %). CONCLUSIONS: Medication-naïve OCD patients seem to remit faster than the previously treated patients. Future prospective naturalistic studies can compare the outcome of medication naïve OCD patients treated with medications and CBT.

Cell cycle abnormality is a cellular phenotype in OCD.

Abnormal indices of cell cycle regulation have been reported in multiple psychiatric disorders. Though reports specific to Obsessive Compulsive Disorder (OCD) are scant, numerous studies have highlighted partly common underlying biology in psychiatric disorders, cell cycle regulation being one such process. In this study, we therefore aimed to explore cell cycle in OCD. To the best of our knowledge, this is the first study to investigate these effects in OCD. We also evaluated the effect of in vitro fluoxetine, commonly used serotonin reuptake inhibitor (SRI) in OCD patients, on cell cycle regulation. The effects of both disease (OCD) and treatment (SRI) were assessed using lymphoblastoid cell lines (LCLs), derived from OCD patients and healthy controls, as a model system. LCLs were treated with 10µM of fluoxetine for 24 h, and the percentage of cells in each phase of the cell cycle was determined by flow cytometry. We observed a lower proportion of cells in the G2/M phase in OCD cases than controls. The findings suggest that cell cycle dysregulation could be peripheral cellular phenotype for OCD. Among cases, all of whom had been systematically characterized for SRI treatment response, LCLs from non-responders to SRI treatment had a lower proportion of cells in G2/M phase than responders.

Impairment of verbal learning and memory and executive function in unaffected siblings of probands with bipolar disorder.

OBJECTIVES: Impairments in executive function and memory have been reported in relatives of patients with bipolar disorder, suggesting that they could be potential endophenotypes for genetic studies, but the findings are inconsistent. In this study, neuropsychological performance in unaffected siblings of probands with family loading for bipolar disorder is compared to that of individually matched healthy controls. We hypothesized that performance on tests of executive functions and memory would be impaired in unaffected siblings of probands with bipolar disorder compared to matched healthy controls. METHODS: We evaluated 30 unaffected siblings of probands with bipolar I disorder and 30 individually matched healthy controls using tests of attention, executive function, and memory. Unaffected siblings and healthy control subjects did not differ with respect to gender, age, and years of education. RESULTS: Unaffected siblings performed poorly on the Tower of London test (TOL), the Rey's auditory verbal learning test (RAVLT), and the Rey's complex figure test. In the multivariate analysis, significance was noted for the TOL, total number of moves (p = 0.007) and the RAVLT total learning score (p = 0.001). CONCLUSIONS: Our study suggests that the deficits in verbal learning and memory and executive functions (planning) could be potential endophenotypes in bipolar disorder. These deficits are consistent with the proposed neurobiological model of bipolar disorder involving the frontotemporal and subcortical circuits. Future studies could couple cognitive and imaging strategies and genomics to identify neurocognitive endophenotypes in bipolar disorder.

Clinical advances in obsessive-compulsive disorder: a position statement by the International College of Obsessive-Compulsive Spectrum Disorders.

In this position statement, developed by The International College of Obsessive-Compulsive Spectrum Disorders, a group of international experts responds to recent developments in the evidence-based management of obsessive-compulsive disorder (OCD). The article presents those selected therapeutic advances judged to be of utmost relevance to the treatment of OCD, based on new and emerging evidence from clinical and translational science. Areas covered include refinement in the methods of clinical assessment, the importance of early intervention based on new staging models and the need to provide sustained well-being involving effective relapse prevention. The relative benefits of psychological, pharmacological and somatic treatments are reviewed and novel treatment strategies for difficult to treat OCD, including neurostimulation, as well as new areas for research such as problematic internet use, novel digital interventions, immunological therapies, pharmacogenetics and novel forms of psychotherapy are discussed.

The prevalence and its correlates of somatization disorder at a quaternary mental health centre.

INTRODUCTION: Somatization Disorder (SD) is known to cause disability and impact the quality of life due to psychological and somatic distress. Though it is a Common Mental Disorder (CMD), the disorder tends to visit all levels of health care, among which prevalence of SD at tertiary care is 10.1%. AIMS: To estimate current prevalence and its correlates of socio-clinical factors in SD at a quaternary mental health centre (QMHC). METHODS: Total of 422 adult subjects were selected through systematic random sampling at first contact psychiatry outpatient clinic. Subjects were interviewed with Mini International Neuropsychiatric Interview Plus version 5.0.0, Clinical Global Impression Severity Scale and Sheehan Disability Scale. RESULTS: Current prevalence of SD was 5%. Significant correlates are observed with median age of 40.5 years, female, married, <5 years of education, monthly income of <₹ 10,357(85.5%) and lower socioeconomic status (75%). DISCUSSION: There is high prevalence of SD even at QMHC. The higher prevalence among adult population in this setup reflect the impairment of working population which invariably impact on national economy. CONCLUSION: Poverty continues to be a major contributing factor to SD causing double impact on the economy by affecting the working population the most.

Neuro-hemodynamic endophenotypes of emotional interference in OCD: fMRI study using emotion counting stroop task.

BACKGROUND: We sought to examine the endophenotype pattern of neuro-hemodynamic substrates of emotion counting Stroop (ecStroop) paradigm in patients with OCD, their unaffected siblings [first degree relatives-FDR] and healthy controls (HC). METHODS: OCD patients (medication naïve)[N = 16], their unaffected siblings(FDR)[N = 16] and HC [N = 24] were compared using an established ecStroop paradigm in a 3-Tesla fMRI. The relative BOLD signals corresponding to the three types of conditions (neural words-N, words with negative emotional salience-E and words with salience for OCD-O) were examined in the apriori hypothesized brain regions. RESULTS: Both in O minus N contrast and O minus E contrast, the groups demonstrated significant differential activation of right insula (BA 13). The post-hoc analyses showed in patients and FDRs relative to HC the following: significant hyperactivation of insula in O minus E contrast; significant hyperactivation of right insula and right DLPFC (BA 9) in O minus N contrast. CONCLUSIONS: The neuro-hemodynamic responses corresponding to the obsessive words in insula and DLPFC could be potential endophenotypes. "Threat relatedness" might thus have a vulnerability meaning in the pathogenesis and neurobiological basis of OCD.

Enhanced error related negativity amplitude in medication-naïve, comorbidity-free obsessive compulsive disorder.

Error monitoring and response inhibition is a key cognitive deficit in obsessive-compulsive disorder (OCD). Frontal midline regions such as the cingulate cortex and pre-supplementary motor area are considered critical brain substrates of this deficit. Electrophysiological equivalent of the above dysfunction is a fronto-central event related potential (ERP) which occurs after an error called the error related negativity (ERN). In this study, we sought to compare the ERN parameters between medication-naïve, comorbidity-free subjects with OCD and healthy controls (HC). Age, sex and handedness matched subjects with medication-naïve, comorbidity-free OCD (N = 16) and Healthy Controls (N = 17) performed a modified version of the flanker task while EEG was acquired for ERN. EEG signals were recorded from the electrodes FCz and Cz. Clinical severity of OCD was assessed using the Yale Brown Obsessive Compulsive Scale. The subjects with OCD had significantly greater ERN amplitude at Cz and FCz. There were no significant correlations between ERN measures and illness severity measures. Overactive performance monitoring as evidenced by enhanced ERN amplitude could be considered as a biomarker for OCD.

Is bipolar II disorder misdiagnosed as major depressive disorder in children?

OBJECTIVES: To estimate the lifetime prevalence of bipolar II disorder in children and adolescents presenting with DSM-IV major depressive disorder (MDD). METHODS: Sixty-one consecutive subjects aged < or =18 years attending the outpatient services of the Child and Adolescent Psychiatric (CAP) services of the National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, India with a diagnosis of MDD were evaluated using the Missouri Assessment of Genetics Interview for children (MAGIC). Two psychiatrists, one of whom was a child psychiatrist diagnosed hypomania by consensus. RESULTS: Twelve children had a past episode of hypomania (20%), which was hitherto undiagnosed clinically. LIMITATIONS: We recruited subjects from a psychiatric hospital, thus limiting the generalizability of the finding. Sample size was relatively small and assessments were cross-sectional. CONCLUSIONS: : Our study shows that bipolar II disorder is often misdiagnosed as MDD in children. The study also highlights that the chance of diagnosing bipolarity is enhanced by using semi-structured interview in routine clinical practice.

Prevalence and correlates of obsessive-compulsive disorder and subthreshold obsessive-compulsive disorder among college students in Kerala, India.

CONTEXT: There are scarce data on the prevalence of adult obsessive-compulsive disorder (OCD) in India. AIMS: The aim was to study the point prevalence of OCD and subthreshold OCD and its psychosocial correlates among college students in the district of Ernakulam, Kerala, India. SETTINGS AND DESIGN: A cross-sectional survey of 5784 students of the age range of 18-25 years from 58 colleges was conducted. MATERIALS AND METHODS: Students were self-administered the OCD subsection of the Clinical Interview Schedule-Revised, the Composite International Diagnostic Interview for obsessive-compulsive symptoms (OCSs), and other relevant instruments to identify OCD, subthreshold OCD, and related clinical measures. STATISTICAL ANALYSIS: The point prevalence of OCD and subthreshold OCD was determined. Categorical variables were compared using Chi-square/Fisher's exact tests as necessary. Differences between means were compared using the ANOVA. RESULTS: The point prevalence of OCD was 3.3% (males = 3.5%; females = 3.2%). 8.5% students (males = 9.9%; females = 7.7%) fulfilled criteria of subthreshold OCD. Taboo thoughts (67.1%) and mental rituals (57.4%) were the most common symptoms in OCD subjects. Compared to those without obsessive-compulsive symptoms (OCSs), those with OCD and subthreshold OCD were more likely to have lifetime tobacco and alcohol use, psychological distress, suicidality, sexual abuse, and higher attention-deficit/hyperactivity disorder symptom scores. Subjects with subthreshold OCD were comparable to those with OCD except that OCD subjects had higher psychological distress scores and academic failures. CONCLUSIONS: OCD and subthreshold OCD are not uncommon in the community, both being associated with significant comorbidity. Hence, it is imperative that both are identified and treated in the community because of associated morbidity.

Association of DRD2 gene variant with schizophrenia.

Schizophrenia is a complex multifactorial disorder for which the pathobiology still remains elusive. Dysfunction of the dopamine D2 receptor signaling has been associated with the illness, but numerous studies provide confounding results. This study investigates the association of synonymous polymorphisms (His313 and Pro319) in the dopamine D2 receptor gene with schizophrenia using a case-control approach, with 101 cases and 145 controls. Our results demonstrated that genotype distribution for the His313 polymorphism was significantly different between schizophrenia patients and control subjects (p=0.0012), while the Pro319 polymorphism did not show any association with the disease. The results suggest that the synonymous SNP His313 in DRD2 may be associated with the illness. However, there is a need for further replication studies with larger sample sets.