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Try to Remember: Interplay between Memory and Substance Use Disorder

Mohamed RMP, Kumar J, Yap E, Mohamed IN, Sidi H, Adam RL, et al.

Curr Drug Targets, 2019;20(2):158-165.
PMID: 28641520 DOI: 10.2174/1389450118666170622092824

Memories associated with substance use disorders, or substance-associated cues increase the likelihood of craving and relapse during abstinence. There is a growing consensus that manipulation of synaptic plasticity may reduce the strength of substance abuse-related memories. On the biological front, there are new insights that suggest memories associated with substance use disorder may follow unique neurobiological pathways that render them more accessible to pharmacological intervention. In parallel to this, research in neurochemistry has identified several potential candidate molecules that could influence the formation and maintenance of long-term memory. Drugs that target these molecules (blebbistatin, isradipine and zeta inhibitory peptide) have shown promise at the preclinical stage. In this review, we shall provide an overview of the evolving understanding on the biochemical mechanisms involved in memory formation and expound on the premise that substance use disorder is a learning disorder.
Fulltext Study of sexual dimorphism of Malaysian crania: an important step in identification of the skeletal remains

Ibrahim A, Alias A, Nor FM, Swarhib M, Abu Bakar SN, Das S

Anat Cell Biol, 2017 Jun;50(2):86-92.
PMID: 28713610 DOI: 10.5115/acb.2017.50.2.86

Sex determination is one of the main steps in the identification of human skeletal remains. It constitutes an initial step in personal identification from the skeletal remains. The aim of the present study was to provide the population-specific sex discriminating osteometric standards to aid human identification. The present study was conducted on 87 (174 sides) slices of crania using postmortem computed tomography in 45 males and 42 females, aged between 18 and 75 years. About 22 parameters of crania were measured using Osirix software 3-D Volume Rendering. Results showed that all parameters were significantly higher in males than in females except for orbital height of the left eye by independent t test (P<0.01). By discriminant analysis, the classification accuracy was 85.1%, and by regression, the classification accuracy ranged from 78.2% to 86.2%. In conclusion, cranium can be used to distinguish between males and females in the Malaysian population. The results of the present study can be used as a forensic tool for identification of unknown crania.
Serotonin Selective Reuptake Inhibitors (SSRIs) and Female Sexual Dysfunction (FSD): Hypothesis on its Association and Options of Treatment

Rappek NAM, Sidi H, Kumar J, Kamarazaman S, Das S, Masiran R, et al.

Curr Drug Targets, 2018;19(12):1352-1358.
PMID: 28025939 DOI: 10.2174/1389450117666161227142947

Sexual dysfunctions are commonly seen in women on selective serotonin reuptake inhibitors (SSRIs). The complexities of female sexual functioning are reflected through modulation of inter- playing factors like the neuropsychophysiological factors, inter-personal and relationship issue, psychiatric co-morbidities and physical disorder. The incidence of SSRIs-induced FSD is difficult to estimate because of the potential confounding effects of SSRIs, presence of polypharmacy, marital effect, socio-cultural factors and due to the design and assessment problems in majority of the studies. The exact mechanism of FSD-induced SSRIs is unknown. It has been postulated that although SSRIs may modulate other neurotransmitter system such as nitric oxide (NO), noradrenergic and dopamine in inducing FSD. In the present review, we highlight current evidence regarding potential mechanism of SSRIs in causing FSD, which include low sexual desire (low libido), arousal difficulties (lack of lubrication), and anorgasmia. The specific association of FSD to SSRI use, has not been ellucidated. The relationship is dose-dependent, and may vary among the groups with respect to mechanism of serotonin and dopamine reuptake, induction of release of prolactin from the pituitary gland, anticholinergic side-effects, inhibition of NO synthesis and emotional-memory circuit encryption for sexual experiences. Various interventional strategies exist regarding the treatment of SSRI-induced FSD and this includes tolerance, titration dosage, substitution to another antidepressant drug and psychotherapy. There is a need of better understanding of SSRIs-induced FSD for better treatment outcome.
Understanding the Pathophysiology of Premature Ejaculation: Bridging the Link between Pharmacological and Psychological Interventions

Yusof F, Sidi H, Das S, Midin M, Kumar J, Hatta MH

Curr Drug Targets, 2018;19(8):856-864.
PMID: 27993112 DOI: 10.2174/1389450117666161215161108

Premature ejaculation (PE) is one of the commonest male sexual dysfunctions. It is characterized by ejaculation which occurs before or soon after vaginal penetration, which causes significant psychological distress to the individual, and his partner. The exact cause of PE is still unknown but several mechanisms are proposed, and these involve complex interactions of neurophysiological, psychosocial, and cognitive factors. We discuss the role of serotonin, nitric oxide, phosphodiesterase enzymes and other neurotransmitters. Treatment of PE tends to co-occur with other sexual difficulties, especially erectile dysfunction (ED). Treatment with selective serotonin reuptake inhibitors (SSRIs) and Dapoxitene are also discussed in detail. The treatment strategy requires a comprehensive holistic approach incorporating both combination of psychopharmacological agent and cognitive-behavioral therapy (CBT). The present review highlights the integration of the hypothalamic-neural and reverberating emotional circuit and discusses the etiology and treatment for patients with PE.
Biological and psychological influences of cross sex hormone in transgender

Ling LS, Sidi H, Lope RAR, Das S, Baharudin A

Curr Drug Targets, 2018 May 11.
PMID: 29749310 DOI: 10.2174/1389450119666180511161420

Transgender is a complex state of bio-psycho-social dimension of human sexuality. It encompasses cognitive-emotional-behavior component that makes the person unique in his or her sexual expression. Transgender tend to use cross sex hormone in order to eradicate their secondary sexual characteristics and to facilitate the shift to their experienced gender. The common masculinising sex hormone use, i.e. Female to Male Treatment Options (FMTO) is testosterone and for feminising hormone i.e. Male to Female Treatment Options (MFTO) is a combination of estrogen with anti-androgen, respectively. Cross sex hormone, i.e. FMTO, or MFTO has biological and psychological influences on the transgender individuals. Nevertheless, cross sex hormone may also poses a range of side effect profiles, varies from the biological to psychosocial impact. The psychological impact can be paramount until it causes severe mental-health problems and even suicide. Numerous ranges of bio-psycho-social influence of cross-sex hormone were highlighted in this review as fundamental core knowledge in the art to know practice when dealing with the treatment options. In psychiatry, the change in the biological appearance may have great influence in the transgender individual, especially in the context of psychosocial and cultural perspective.
Fulltext Peripheral Demyelinating Diseases: From Biology to Translational Medicine

Kamil K, Yazid MD, Idrus RBH, Das S, Kumar J

Front Neurol, 2019;10:87.
PMID: 30941082 DOI: 10.3389/fneur.2019.00087

Demyelinating diseases represent a spectrum of disorders that impose significant burden on global economy and society. Generally, the prognosis of these diseases is poor and there is no available cure. In recent decades, research has shed some light on the biology and physiology of Schwann cells and its neuroprotective effects in the peripheral nervous system (PNS). Insults to the PNS by various infectious agents, genetic predisposition and immune-related mechanisms jeopardize Schwann cell functions and cause demyelination. To date, there are no effective and reliable biomarkers for PNS-related diseases. Here, we aim to review the following: pathogenesis of various types of peripheral demyelinating diseases such as Guillain-Barre syndrome, Chronic Inflammatory Demyelinating Polyradiculoneuropathy, Anti-Myelin Associated Glycoprotein Neuropathy, POEMS syndrome, and Charcot-Marie-Tooth disease; emerging novel biomarkers for peripheral demyelinating diseases, and Schwann cell associated markers for demyelination.
Antimicrobial Exploration Between Counterpart Endosymbiont and Host Plant (Tamarindus indica Linn.)

Chigurupati S, Vijayabalan S, Selvarajan KK, Aldubayan M, Alhowail A, Mani V, et al.

Curr Pharm Biotechnol, 2020;21(5):384-389.
PMID: 31657678 DOI: 10.2174/1389201020666191028105325

BACKGROUND: Endophytic bacteria produce various bioactive secondary metabolites, which benefit human health. Tamarindus indica L. is well known for its medicinal value in human health care. Several studies have reported on its biological effects from various parts of T. indica, but only a few studies have been devoted to examining the biological activity of endophytes of T. indica.
OBJECTIVES: In the present study, an endophyte was isolated from the leaves of T. indica and screened for its antimicrobial potential.
METHODS: The selected endophyte was identified by 16s rRNA partial genome sequencing and investigated for their antimicrobial potency. The preliminary phytochemical tests were conducted for the affirmation of phytoconstituents in the endophytic crude ethyl acetate extract of T. indica (TIM) and total phenolic content was performed. The antimicrobial potential of TIM was evaluated against human pathogenic ATCC gram-positive and gram-negative bacterial strains.
RESULTS: TIM exhibited an appreciable amount of gallic acid equivalent phenolic content (21.6 ± 0.04 mg GAE/g of crude extract). TIM showed the Minimum Inhibitory Concentration (MIC) at 250 μg/mL and Minimum Bactericidal Concentration (MBC) at 500 μg/mL among the selected human pathogenic ATCC strains. At MIC of 500 μg/mL, TIM displayed a significant zone of inhibition against P. aeruginosa and N. gonorrhoeae.
CONCLUSION: The results from our study highlighted for the first time the antimicrobial potential of endophytic bacterial strain Bacillus velezensis in T. indica leaves and it could be further explored as a source of natural antimicrobial agents.
Fulltext Functional Outcome of Modified Brostrom-Gould Procedure Using the PopLok Knotless Suture Anchor Technique in Lateral Ankle Instability

Bajuri MY, Daun E, Abdul Raof MH, Hassan MR, Das S

Cureus, 2019 Jun 22;11(6):e4971.
PMID: 31497416 DOI: 10.7759/cureus.4971

Introduction The modified Brostrom-Gould procedure is surgery to repair the lateral ligamentous complex of an ankle with chronic instability. A retrospective study was carried out among patients who had undergone this procedure at a medical center. Aim The aim of the study was to determine the mid-term functional outcome and rate of infection among patients who underwent the surgery using the PopLok® (CONMED, NY, US) Knotless Suture Anchor technique for lateral ankle instability. Methods Twenty patients who failed conservative treatment at the Universiti Kebangsaan Malaysia Medical Centre (UKMMC), Kuala Lumpur, and who were operated on by a single surgeon from January 2011 until March 2015 were selected to participate in this study. They were examined clinically both preoperatively and postoperatively and were also evaluated using the American Foot and Ankle Score (AOFAS) and the Visual Analogue Scale (VAS). The last review of the patients, for the purpose of this study, was done at one-year postoperatively. Results The patients' overall AOFAS and VAS scores improved postoperatively as compared to the preoperative period. Preoperatively, the mean AOFAS score was 63.5 while postoperatively, the score was 93.50 (excellent score 90 - 100). The mean VAS score was 8.00 preoperatively and improved to 1.00 postoperatively. There was also an absence of infection observed one-year post-surgery. Conclusion The modified Brostrom-Gould procedure using the PopLok® Knotless Suture Anchor technique provides an excellent middle-term functional outcome and a reduction in pain for patients who failed conservative treatment, with a very low rate of infection.
Fulltext Consequences of Circadian Disruption in Shift Workers on Chrononutrition and their Psychosocial Well-Being

Mohd Azmi NAS, Juliana N, Mohd Fahmi Teng NI, Azmani S, Das S, Effendy N

Int J Environ Res Public Health, 2020 03 19;17(6).
PMID: 32204445 DOI: 10.3390/ijerph17062043

The workers and employees in various institutions are subjected to different shifts and work schedules. The employees work not only at daytime but also during odd hours at night. The biological clock of an individual is often altered during night shifts. This affects the psychosocial well-being and circadian nutritional intake of the worker. Disturbance in circadian rhythm results in the development of metabolic disorders such as hypertension, dyslipidemia, dysglycemia, and abdominal obesity. In the present review, we discuss the nature of shift work, sleep/wake cycle of an individual, chrononutrition, dietary habits, and meal changes with regard to timing and frequency, related to shift work. We also discuss the relationship between nutritional intake and psychosocial well-being among shift workers. The review may be beneficial for prevention of metabolic disorders and maintaining sound psychological condition in shift workers.
mTORC and PKCε in Regulation of Alcohol Use Disorder

Hanim A, Mohamed IN, Mohamed RMP, Das S, Nor NSM, Harun RA, et al.

Mini Rev Med Chem, 2020;20(17):1696-1708.
PMID: 32579497 DOI: 10.2174/1389557520666200624122325

Alcohol use disorder (AUD) is characterized by compulsive binge alcohol intake, leading to various health and social harms. Protein Kinase C epsilon (PKCε), a specific family of PKC isoenzyme, regulates binge alcohol intake, and potentiates alcohol-related cues. Alcohol via upstream kinases like the mammalian target to rapamycin complex 1 (mTORC1) or 2 (mTORC2), may affect the activities of PKCε or vice versa in AUD. mTORC2 phosphorylates PKCε at hydrophobic and turn motif, and was recently reported to be associated with alcohol-seeking behavior, suggesting the potential role of mTORC2-PKCε interactions in the pathophysiology of AUD. mTORC1 regulates translation of synaptic proteins involved in alcohol-induced plasticity. Hence, in this article, we aimed to review the molecular composition of mTORC1 and mTORC2, drugs targeting PKCε, mTORC1, and mTORC2 in AUD, upstream regulation of mTORC1 and mTORC2 in AUD and downstream cellular mechanisms of mTORCs in the pathogenesis of AUD.
Fulltext Synergetic Effects of Hybrid Carbon Nanostructured Counter Electrodes for Dye-Sensitized Solar Cells: A Review

Samantaray MR, Mondal AK, Murugadoss G, Pitchaimuthu S, Das S, Bahru R, et al.

Materials (Basel), 2020 Jun 19;13(12).
PMID: 32575516 DOI: 10.3390/ma13122779

This article provides an overview of the structural and physicochemical properties of stable carbon-based nanomaterials and their applications as counter electrodes (CEs) in dye-sensitized solar cells (DSSCs). The research community has long sought to harvest highly efficient third-generation DSSCs by developing carbon-based CEs, which are among the most important components of DSSCs. Since the initial introduction of DSSCs, Pt-based electrodes have been commonly used as CEs owing to their high-electrocatalytic activities, thus, accelerating the redox couple at the electrode/electrolyte interface to complete the circuit. However, Pt-based electrodes have several limitations due to their cost, abundance, complicated facility, and low corrosion resistance in a liquid electrolyte, which further restricts the large-area applications of DSSCs. Although carbon-based nanostructures showed the best potential to replace Pt-CE of DSSC, several new properties and characteristics of carbon-CE have been reported for future enhancements in this field. In this review, we discuss the detailed synthesis, properties, and performances of various carbonaceous materials proposed for DSSC-CE. These nano-carbon materials include carbon nanoparticles, activated carbon, carbon nanofibers, carbon nanotube, two-dimensional graphene, and hybrid carbon material composites. Among the CE materials currently available, carbon-carbon hybridized electrodes show the best performance efficiency (up to 10.05%) with a high fill factor (83%). Indeed, up to 8.23% improvements in cell efficiency may be achieved by a carbon-metal hybrid material under sun condition. This review then provides guidance on how to choose appropriate carbon nanomaterials to improve the performance of CEs used in DSSCs.
Association of Micro RNA and Postoperative Cognitive Dysfunction: A Review

Yazit NAA, Juliana N, Das S, Teng NIMF, Fahmy NM, Azmani S, et al.

Mini Rev Med Chem, 2020;20(17):1781-1790.
PMID: 32564754 DOI: 10.2174/1389557520666200621182717

Postoperative Cognitive Dysfunction (POCD) refers to the condition of neurocognitive decline following surgery in a cognitive and sensory manner. There are several risk factors, which may be life-threatening for this condition. Neuropsychological assessment of this condition is very important. In the present review, we discuss the association of apolipoprotein epsilon 4 (APOE ε4) and few miRNAs with POCD, and highlight the clinical importance for prognosis, diagnosis and treatment of POCD. Microarray is a genome analysis that can be used to determine DNA abnormalities. This current technique is rapid, efficient and high-throughout. Microarray techniques are widely used to diagnose diseases, particularly in genetic disorder, chromosomal abnormalities, mutations, infectious diseases and disease-relevant biomarkers. MicroRNAs (miRNAs) are a class of non-coding RNAs that are widely found distributed in eukaryotes. Few miRNAs influence the nervous system development, and nerve damage repair. Microarray approach can be utilized to understand the miRNAs involved and their pathways in POCD development, unleashing their potential to be considered as a diagnostic marker for POCD. This paper summarizes and identifies the studies that use microarray based approaches for POCD analysis. Since the application of microarray in POCD is expanding, there is a need to review the current knowledge of this approach.
Fulltext Construction of an Affordable Open-Design Recirculating Zebrafish Housing System

Teoh SL, Sapri SRB, Yusof MRBM, Yahaya MF, Das S

J Am Assoc Lab Anim Sci, 2020 09 01;59(5):512-518.
PMID: 32600503 DOI: 10.30802/AALAS-JAALAS-19-000167

Recently, the zebrafish has gained in popularity as a vertebrate animal model for biomedical research. Commercial zebrafish housing systems are available and are designed to maximize stocking density of fish for a given space, but these systems are expensive and purchasing them may not be feasible for emerging laboratories with limited funding. In this article, we describe the construction of a simple and affordable recirculating zebrafish housing system. This system can be constructed in 3 working days, with materials readily available in hardware stores. The cost for construction of the system was only 3,000 MYR (750 USD). The system consists of a water reservoir, a supply line that delivers water to the shelves holding the zebrafish tanks, and a drainage line that receives water from both the supply line and the shelves containing the fish tanks and returns this water to the reservoir. This system also has a 3-stage filtration process to ensure that clean water is delivered to the zebrafish tank. The system can house up to 360 zebrafish. This low-cost housing system may make research using zebrafish feasible some laboratories.
Fulltext Effect of intercostal stretch on pulmonary function parameters among healthy males

Mohan V, Aziz KB, Kamaruddin K, Leonard JH, Das S, Jagannathan MG

EXCLI J, 2012;11:284-90.
PMID: 27418905

The use of manual stretching procedures has become more prevalent in cardiorespiratory physiotherapy to improve pulmonary functions. However, limited evidence exists regarding evaluation of their effectiveness. The study aimed to determine the impact of Intercostal (IC) stretch in improving the dynamic pulmonary function parameters (Forced Expiratory Volume in the first second (FEV1), Forced Vital Capacity (FVC) and FEV1/FVC % and respiratory rate among healthy adults. Thirty healthy male subjects were recruited based on inclusion and exclusion criteria. Subjects were assigned to the experimental group and the control group through random sampling method. In the experimental group, subjects underwent IC stretch for ten breaths on the inspiratory phase of the respiratory cycle with breathing control exercises in semi recumbent position, while in the control group, breathing control exercises alone were performed in the semi recumbent position. The results of the study showed, FEV1/FVC % in the experimental group significantly improved with P=0.017 (p<0.05) than the control group, which means IC stretch increased lung volume and lead to improved lung function. This study suggested the IC stretching with breathing control may be more effective in improving dynamic lung parameters especially FEV1/FVC % than breathing control alone.
Effect of methanolic extract of Piper sarmentosum leaves on neointimal foam cell infiltration in rabbits fed with high cholesterol diet

Amran AA, Zakaria Z, Othman F, Das S, Al-Mekhlafi HM, Raj S, et al.

EXCLI J, 2012;11:274-83.
PMID: 27366140

Previous research has shown the beneficial effects of aqueous extract of Piper sarmentosum (P.s) on atherosclerosis. The first stage in atherosclerosis is the formation of foam cell. The aim of this study was to investigate the effect of the methanol extract of P.s on fatty streaks by calculating neointimal foam cell infiltration in rabbits fed with high cholesterol diet. Thirty six male New Zealand white rabbits were divided equally into six groups: (i) C: control group fed normal rabbit chow; (ii) CH: cholesterol diet (1 % cholesterol); (iii) PM1: 1 % cholesterol with methanol extract of P.s (62.5 mg/kg); (iv) PM2: 1 % cholesterol with methanol extract of P.s (125 mg/kg); (v) PM3: 1 % cholesterol with methanol extract of P.s (250 mg/kg); (vi) SMV group fed 1 % cholesterol supplemented with Simvistatin drug (1.2 mg/kg). All animals were treated for 10 weeks. At the end of the treatment, the rabbits were fasted and sacrificed and the aortic tissues were collected for histological studies to measure the area of the neointimal foam cell infiltration using software. The thickening of intima ratio of atherosclerosis and morphological changes by scanning electron microscope were measured. The results showed that the atherosclerotic group had significantly bigger area of fatty streak compared to the control group. The area of fatty streak in the abdominal aorta was significantly reduced in the treatment groups which were similar with the SMV group. Similarly, there was a reduction in the number of foam cell in the treatment groups compared to the atherosclerotic group as seen under scanning microscope. In conclusion, histological study demonstrated that the methanol extract of the P.s could reduce the neointimal foam cell infiltration in the lumen of the aorta and the atherosclerotic lesion.
Protective effect of curcumin on experimentally induced arthritic rats: detailed histopathological study of the joints and white blood cell count

Kamarudin TA, Othman F, Mohd Ramli ES, Md Isa N, Das S

EXCLI J, 2012;11:226-36.
PMID: 27366139

Curcuma longa (turmeric) rhizomes contains curcumin, an active compound which possesses anti-inflammatory effects. Collagen-induced arthritis (CIA) is an accepted experimental animal model of rheumatoid arthritis. The present study aimed to observe the histological changes in the joints of experimental arthritic rats treated with curcumin. Twenty four male Sprague-Dawley (approximately 7 weeks-old) rats were randomly divided into four groups. Three groups were immunized with 150 µg collagen. All rats with established CIA, with arthritis scores exceeding 1, were orally treated with betamethasone (0.5 mg/ml/kg body weight), curcumin (110 mg/ml/kg body weight) or olive oil (1.0 ml/kg body weight) daily, for two weeks. One remaining group was kept as normal control. Treatment with 110 mg/ml/kg curcumin showed significant mean differences in the average white blood cell (WBC) count (p<0.05), cell infiltration, bone and cartilage erosion scores (p<0.05) compared to the olive oil treated group. Pannus formation scores showed that curcumin supplementation successfully suppressed the pannus formation process that occurred in the articular cartilage of the CIA joints. The mean difference for histological scores for the curcumin group was insignificant compared to the betamethasone treated group. It is concluded that supplementation of curcumin has protective effect on the histopathological and degenerative changes in the joints of CIA rats which was at par with betamethasone.
The Phosphodiasterase 5-Inhibitors (PDE-5i) for Erectile Dysfunction (ED): A Therapeutic Challenge For Psychiatrists

Koon CS, Sidi H, Kumar J, Xi OW, Das S, Hatta MH, et al.

Curr Drug Targets, 2018;19(12):1366-1377.
PMID: 28215172 DOI: 10.2174/1389450118666170215164747

Erectile function (EF) is a prerequisite for satisfactory sexual intercourse (SI) and central to male sexual functioning. Satisfactory SI eventually initiates orgasm - a biopsychophysiological state of euphoria - leading to a sense of bliss, enjoyment and positive mental well being. For a psychiatrist, treating ED is self-propelled to harmonize these pleasurable experiences alongside with encouragement of physical wellness and sensuality. Hence, the role of PDE-5i is pivotal in this context and constitutes a therapeutic challenge. PDE-5i work via the dopaminergic-oxytocin-nitric oxide pathway by increasing the availability of endothelial's guanosine monophosphate (GMP), immediately causing relaxation of the penile smooth muscle and an erection. The PDE-5i, like sildenafil, vardenafil and tadalafil, are effective in the treatment of ED with some benefits/ flexibilities and disadvantages compared to other treatment modalities. Prescribed PDE-5i exclusively improve EF, fostering male's self-confidence and self-esteem. Treatment failures are associated with factors such as absent (or insufficient) sexual stimulation, psychosexual conflicts and the co-existence of medical disorders. Managing ED requires dealing with underlying medical diseases, addressing other co-morbid sexual dysfunctions like premature ejaculation (PE), and educating the patient on healthy life-styles. Furthermore, by dealing with interpersonal dynamics within the couple and embracing adequate lifestyles (managing stress and revising one's sexual scripts), PDE-5i treatment benefits may be enhanced. In this review, we propose a holistic conceptual framework approach for psychiatric management of patients with ED.
The Neurobiology and Psychiatric Perspective of Vaginismus: Linking the Pharmacological and Psycho-Social Interventions

Kadir ZS, Sidi H, Kumar J, Das S, Midin M, Baharuddin N

Curr Drug Targets, 2018;19(8):916-926.
PMID: 28228081 DOI: 10.2174/1389450118666170222153908

Vaginismus is an involuntary muscle contraction of the outer third of vaginal barrel causing sexual penetration almost impossible. It is generally classified under sexual pain disorder (SPD). In Diagnostic and Statistical Manual, 5th edition (DSM-5), it is classified under the new rubric of Genito-Pelvic Pain/Sexual Penetration Disorder. This fear-avoidance condition poses an ongoing significant challenge to the medical and health professionals due to the very demanding needs in health care despite its unpredictable prognosis. The etiology of vaginismus is complex: through multiple biopsycho- social processes, involving bidirectional connections between pelvic-genital (local) and higher mental function (central regulation). It has robust neural and psychological-cognitive loop feedback involvement. The internal neural circuit involves an inter-play of at least two-pathway systems, i.e. both "quick threat assessment" of occipital-limbic-occipital-prefrontal-pelvic-genital; and the chronic pain pathways through the genito-spinothalamic-parietal-pre-frontal system, respectively. In this review, a neurobiology root of vaginismus is deliberated with the central role of an emotional-regulating amygdala, and other neural loop, i.e. hippocampus and neo-cortex in the core psychopathology of fear, disgust, and sexual avoidance. Many therapists view vaginismus as a neglected art-and-science which demands a better and deeper understanding on the clinico-pathological correlation to enhance an effective model for the bio-psycho-social treatment. As vaginismus has a strong presentation in psychopathology, i.e. fear of penetration, phobic avoidance, disgust, and anticipatory anxiety, we highlighted a practical psychiatric approach to the clinical management of vaginismus, based on the current core knowledge in the perspective of neuroscience.
Hypersexuality As a Neuropsychiatric Disorder: The Neurobiology and Treatment Options

Asiff M, Sidi H, Masiran R, Kumar J, Das S, Hatta NH, et al.

Curr Drug Targets, 2018;19(12):1391-1401.
PMID: 28325146 DOI: 10.2174/1389450118666170321144931

Hypersexuality refers to abnormally increased or extreme involvement in any sexual activity. It is clinically challenging, presents trans-diagnostically and there is extensive medical literature addressing the nosology, pathogenesis and neuropsychiatric aspects in this clinical syndrome. Classification includes deviant behaviours, diagnosable entities related to impulsivity, and obsessional phenomena. Some clinicians view an increase in sexual desire as 'normal' i.e. psychodynamic theorists consider it as egodefensive at times alleviating unconscious anxiety rooted in intrapsychic conflicts. We highlight hypersexuality as multi-dimensional involving an increase in sexual activity that is associated with distress and functional impairment. The aetiology of hypersexuality is multi-factorial with differential diagnoses that include major psychiatric disorders (e.g. bipolar disorder), adverse effects of treatments (e.g. levodopatreatment), substance-induced disorders (e.g. amphetamine substance use), neuropathological disorders (e.g. frontal lobe syndrome), among others. Numerous neurotransmitters are implicated in its pathogenesis, with dopamine and noradrenaline playing a crucial role in the neural reward pathways and emotionally- regulated limbic system neural circuits. The management of hypersexuality is determined by the principle of de causa effectu evanescent, if the causes are treated, the effect may disappear. We aim to review the role of pharmacological agents causing hypersexuality and centrally acting agents treating the associated underlying medical conditions. Bio-psycho-social determinants are pivotal in embracing the understanding and guiding management of this complex and multi-determined clinical syndrome.
Co-Morbid Erectile Dysfunction (ED) and Antidepressant Treatment in a Patient - A Management Challenge?

Zainol M, Sidi H, Kumar J, Das S, Ismail SB, Hatta MH, et al.

Curr Drug Targets, 2019;20(2):182-191.
PMID: 28302034 DOI: 10.2174/1389450118666170315110902

Throughout the world, antidepressants (AD) and phosphodiesterase-5 inhibitors (PDE-5i) are the commonly prescribed psychopharmacological agents for treating patients with co-morbid mental health problem and sexual dysfunction (SD). The serotonergic and noradrenergic ADs, although effective, are not without any SD adverse-effects, especially erectile dysfunction (ED). ED is a failure to obtain a satisfactory erection for rewarding sexual coitus during the phases of male's sexual arousal. It is recognized as an important reason why non-adherence to treatment was observed in patients who were on AD. AD intervention caused remission to some of the pre- treatment psychopathology of ED. However, in many patients, AD potentially magnified the unwanted sexual sideeffects. This made the situation challenging for the mental health professional. These challenges are based on the complexity of ED, its etiology and the associated risk factors, which further add to its AD side-effect. The neuro-psychopharmacological basis for AD treatment selection was deliberated. Bio-psycho-social interventions are recommended at two pivotal stages. Firstly, a step should be taken for proper assessment (e.g. detailed history, psychosocial and laboratory investigations); and identify few modifiable risk factors for ED and associated mental health issues. Secondly, with guidance of an algorithm pathway, a practical intervention should include strategies such as dose reduction, augmentation or changing to an AD with lesser or no sexual adverse-effects. It is recommended that bupropion and mirtazepine to be prescribed when patients develop adverse sexual effects with serotonin selective reuptake inhibitor (SSRI), serotonin norepinephrine reuptake inhibitor (SNRI) and tricyclic antidepressant (TCA). Few suggestions which may be borne in mind are revising sexual scripts and improving sexual techniques, life-style modifications, psychotherapy and other nonpharmacological approaches which may be beneficial to both patients and their partners.

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